Startseite circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
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circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis

  • Rui Tian , Huixin Li , Songjie Ren , Shukui Li , Run Fang und Yang Liu EMAIL logo
Veröffentlicht/Copyright: 14. Juli 2023
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Open Medicine
Aus der Zeitschrift Open Medicine Band 18 Heft 1

Abstract

Circular RNA (circRNA) THBS1 has been shown to exist as an oncogene in non-small-cell lung cancer, but its role in cervical cancer is still unclear. Our experiment aimed to uncover the functions and specific mechanism of circRNA THBS1 in cervical cancer cells. Levels of circRNA THBS1 and miR-543 in cervical cancer tissues and cell lines were assessed by RT-qPCR. starBase and dual luciferase reporter gene assay were applied for investigating the correlation between miR-543 and circRNA THBS1/HMGB2. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry, respectively. Furthermore, the levels of HMGB2, E-cadherin, and N-cadherin in HeLa cells were determined by RT-qPCR and western blot analysis. Our data revealed that circRNA THBS1 was significantly upregulated and miR-543 was low expressed in cervical cancer tissues and cell lines. circRNA THBS1 interacted with miR-543 and negatively regulated miR-543 expression in HeLa cells. Silencing of circRNA THBS1 remarkably suppressed HeLa cells’ viability, accelerated cells’ apoptosis, and inhibited the EMT of HeLa cells, while these changes were reversed by miR-543 inhibitor. Moreover, miR-543 affected HeLa cells by targeting HMGB2. In conclusion, circRNA THBS1 silencing inhibited the malignant biological behaviors of cervical cancer cells via the regulation of miR-543/HMGB2 axis.

Keywords: circRNA THBS1; cervical cancer cells; miR-543/HMGB2 axis

1 Introduction

Cervical cancer is the most common gynecological malignancy, which has become a major health problem for women. Women with early marriage, early childbirth, fertility, and sexual disorders have a higher prevalence rate [1,2]. At present, surgery, chemotherapy, radiotherapy, and targeted therapy were applied for cervical cancer treatment [3,4]. However, the cure rate of middle- and late-stage cervical cancer patients is very low. Therefore, the basic research on the pathogenesis of cervical cancer is of great significance to improve the level of clinical treatment. In particular, it is necessary to explore the biological functions and regulatory effects of cervical cancer-related genes, study the molecular mechanisms related to the occurrence and development of cervical cancer, and seek therapeutic targets for cervical cancer.

Circular RNA (circRNA) is a new type of non-coding RNA molecule with closed circular structure [5]. Increasing reports have confirmed that circRNA plays an important regulatory role in the occurrence, development, and metastasis of tumors [6,7]. Therefore, cyclic RNA has the potential to become a biomarker for tumor diagnosis and a new target for treatment. A study has shown that circRNA THBS1 promotes the migration and invasion of non-small-cell lung cancer cells by adsorbing the expression of miR-129-5p regulating gene SOX4 [8]. However, the role and mechanism of circRNA THBS1 in cervical cancer is still unclear. It is necessary to further study the effect of circRNA THBS1 in cervical cancer cells and analyze the potential molecular regulation mechanism.

microRNA (miRNA) is a kind of endogenous non-coding RNA with a length of about 19–25 nt, which is widely involved in post-transcriptional regulation of genes [9]. Recent studies have shown that miRNA is involved in a variety of regulatory pathways, including organ formation, cell proliferation and apoptosis, fat metabolism, and so on, and plays an important role in gene expression regulation [10,11]. In various cancers, miRNA may act as a carcinogen or tumor suppressor to regulate tumor formation. miR-543 has been shown to promote cell proliferation and metastasis of renal cell carcinoma through Wnt/β-Catenin signaling pathway [12]. Besides, miR-543 promotes the proliferation and metastasis of colorectal cancer by targeting KLF4 [13]. Moreover, it was found that miR-543 was significantly downregulated in cervical cancer, and it played an anti-cancer role in cervical cancer [14]. Therefore, we hypothesized that circRNA THBS1 may play a role in cervical cancer by regulating the expression of miR-543.

Thus, our investigation aimed to explain the underlying functions of circRNA THBS1 and miR-543 in cervical cancer and elucidate latent mechanisms.

2 Materials and methods

2.1 Clinical specimen collection

Thirty pairs of cancerous tissues and adjacent normal tissues from patients with cervical cancer were collected at the Shanghai Mengchao Cancer Hospital. All specimens were rapidly frozen and stored in liquid nitrogen and preserved at −80°C for further analysis. The research procedure was approved by the ethics committee of Shanghai Mengchao Cancer Hospital. We obtained the written informed consent of all patients, and all patients agree to use tissue in the study.

2.2 Cell culture

Normal human cervical epithelial cell line (Ect1/E6E7) and cervical cancer cell lines (C-33A, SiHa, CaSki, and HeLa) were purchased from ATCC. The cells were cultivated in RPMI-1640 medium (Procell) containing 15% FBS (Procell) and 1% penicillin/streptomycin (Procell) in a humidified incubator containing 5% CO2 at 37°C.

2.3 Dual-luciferase reporter assay

starBase was used to identify the relationship between circRNA THBS1 and miR-543. The results indicated that miR-543 was the potential target of circRNA THBS1. The fragment of the circRNA THBS1 containing the miR-543-binding site or mutate target site was amplified by RT-PCR and then cloned into a pmirGLO vector (Promega, USA) to generate the reporter vector circRNA THBS1 wild type (circRNA THBS1-WT) or circRNA THBS1 mutated type (circRNA THBS1-MUT). circRNA THBS1-WT or circRNA THBS1-MUT and miR-543 mimics or mimic control were co-transfected into 293T cells using Lipofectamine 3000, respectively, and incubated for 48 h. Then, the relative luciferase activity was detected by Dual-Luciferase® Reporter Assay System (Promega, USA) following the protocol. The relationship between miR-543 and HMGB2 was verified using the same method.

2.4 RT-qPCR analysis

After treatment, the levels of circRNA THBS1, miR-543, HMGB2, E-cadherin, and N-cadherin were measured by RT-qPCR. The isolation of RNA from cervical cancer tissue and cervical cancer cell lines (C-33A, SiHa, CaSki, and HeLa) was obtained with the TRIpure Total RNA Extraction Reagent (ELK Biotechnology) based on the protocol. Then, the total RNA was reversed to cDNA following the instructions of PrimeScript RT Reagent Kit (TaKaRa, China), and qPCR analysis was conducted using the SYBR PrimeScript RT-PCR Kit (TaKaRa) with ABI 7500 Real-Time PCR System (Agilent Technologies, USA). Target gene expressions were calculated using the 2−ΔΔCt method.

2.5 Cell transfection

Control-siRNA, circRNA THBS1-siRNA, control plasmid, circRNA THBS1 plasmid, inhibitor control, miR-543 inhibitor, mimic control, miR-543 mimic, control plasmid, or HMGB2 plasmid were transfected into HeLa cells by Lipofectamine 3000 (Invitrogen) for 48 h referring to the instructions. After 48 h transfection, RNA was extracted for RT-qPCR analysis, and western blot was adapted to evaluate the protein expression.

2.6 MTT assay

After treatment, HeLa cells were implanted into 96-well plates and treated with 10 μl MTT solution and continuously incubated for further 4 h. Then, the supernatant was discarded and 100 μl of DMSO was added to dissolve lysate. Finally, the optical density at the wavelength of 570 nm was measured by a microplate reader (BIOTEK, USA) following the protocol.

2.7 Flow cytometry (FCM) assay

After digesting the cells with trypsin without EDTA, the HeLa cells were collected by centrifugation at 4°C for 5 min. After that, the cells were washed twice with pre-cooled PBS. Then 1× binding buffer was used to prepare cell suspension. For cell apoptosis assay, cells were assessed using the Annexin-V/propidium iodide Apoptosis Detection Kit (Beyotime) according to the manufacturer’s protocol. Finally, apoptotic cells were checked using a Flow cytometer (BD Biosciences) and analyzed with Kaluza Analysis software (version 2.1.1.20653; Beckman Coulter, Inc.).

2.8 Western blot assay

The HeLa cells were lysed using RIPA buffer (Beyotime) for 30 min on ice. Proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then transferred onto polyvinylidene fluoride membranes. The membranes were blocked with 5% skimmed milk for 2 h to avoid nonspecific binding and then cultivated with primary antibodies against E-cadherin, N-cadherin, or GAPDH (1:1,000 dilution) at 4°C overnight. After washing in TBST, the membranes were cultivated with secondary antibodies for 2 h. The protein signals were assessed by electrogenerated chemiluminescence method following the instructions.

2.9 Statistical analysis

All the above experiments were performed three times. All results were presented as the mean ± standard deviation and analyzed by using GraphPad Prism 6.0. Differences among groups were estimated using one-way analysis of variance and Student’s t-test. *P < 0.05, and **P < 0.01 indicated statistically as significant difference.

3 Results

3.1 MiR-543 directly interacted with circRNA THBS1

We first explored the relevance between circRNA THBS1 and miRNAs, and the bioinformatics analysis (starBase) suggested that circRNA THBS1 harbored a binding site for miR-543 (Figure 1a). Dual-luciferase reporter assay further evidenced that miR-543 mimic remarkably reduced the relative luciferase activity of circRNA THBS1-WT, while the luciferase activity of circRNA THBS1-MUT was unaffected (Figure 1b). We also performed the dual luciferase reporter assay in HeLa cells, and similar results were obtained (Figure A1a). Moreover, we illustrated the effects of miR-543 on circRNA THBS1 in HeLa cells, and HeLa cells were transfected with mimic control and miR-543 mimic. The data indicated that compared with the mimic control group, miR-543 significantly enhanced miR-543 expression in HeLa cells (Figure 1c). However, miR-543 mimic had no significat effects on circRNA THBS1 expression in HeLa cells (Figure 1d). These findings demonstrated that circRNA THBS1 sponged miR-543 in the progression of cervical cancer.

Figure 1 circRNA THBS1 sponged to miR-543. (a) The predicted binding site for miR-543 in the 3′-UTR of circRNA THBS1. (b) Luciferase activities were evaluated using Dual luciferase reporter assay in 293T cells. (c) Relative expression level of miR-543 in miR-543 mimic-transfected HeLa cells. (d) Relative expression level of circRNA THBS1 in miR-543 mimic-transfected cells. **P < 0.01 vs mimic control.
Figure 1

circRNA THBS1 sponged to miR-543. (a) The predicted binding site for miR-543 in the 3′-UTR of circRNA THBS1. (b) Luciferase activities were evaluated using Dual luciferase reporter assay in 293T cells. (c) Relative expression level of miR-543 in miR-543 mimic-transfected HeLa cells. (d) Relative expression level of circRNA THBS1 in miR-543 mimic-transfected cells. **P < 0.01 vs mimic control.

3.2 CircRNA THBS1 was significantly upregulated and miR-543 was low-expressed in cervical cancer patient tissues and cervical cancer cell lines

We then analyzed the circRNA THBS1 and miR-543 expression in cervical cancer tissues and cell lines. RT-qPCR analysis revealed that circRNA THBS1 was upregulated and miR-543 was downregulated in cervical cancer patient tissues (Figure 2a and b), compared to normal paracancer tissues. As displayed in Figure 2c, the level of circRNA THBS1 was obviously higher in cervical cancer cell lines than that in Ect1/E6E7 cells. Besides, we observed that miR-543 was downexpressed in cervical cancer cell lines, as opposed to Ect1/E6E7 cells (Figure 2d). Our findings suggested that circRNA THBS1/miR-543 may play a regulatory role in cervical cancer. Due to the more significant difference in the expression of circRNA THBS1/miR-543 in the cervical cancer cell line HeLa, we thus choose HeLa cells for further research.

Figure 2 Expression of circRNA THBS1 and miR-543 in cervical cancer tissues and cells. RT-qPCR analysis of circRNA THBS1 (a) and miR-543 (b) expression in cervical cancer tissues and adjacent normal tissues. (c and d) Detection of circRNA THBS1 and miR-543 in cervical cancer cell line (C-33A, SiHa, CaSki, and HeLa) and Ect1/E6E7 cells. **P < 0.01 vs adjacent normal tissue; ## P < 0.01 vs Ect1/E6E7.
Figure 2

Expression of circRNA THBS1 and miR-543 in cervical cancer tissues and cells. RT-qPCR analysis of circRNA THBS1 (a) and miR-543 (b) expression in cervical cancer tissues and adjacent normal tissues. (c and d) Detection of circRNA THBS1 and miR-543 in cervical cancer cell line (C-33A, SiHa, CaSki, and HeLa) and Ect1/E6E7 cells. **P < 0.01 vs adjacent normal tissue; ## P < 0.01 vs Ect1/E6E7.

3.3 CircRNA THBS1 negatively regulated miR-543 expression in cervical cancer cell line HeLa

To further explain the regulatory roles of circRNA THBS1 and miR-543 in cervical cancer cells, control-siRNA, circRNA THBS1-siRNA, inhibitor control, or miR-543 inhibitor were transfected into HeLa cells for 48 h. RT-qPCR assay was applied to detect circRNA THBS1 and miR-543 levels in different groups. Our data revealed that circRNA THBS1-siRNA remarkably decreased circRNA THBS1 levels, compared to the control-siRNA group (Figure 3a). Furthermore, as displayed in Figure 3b, miR-543 was downregulated in miR-543 inhibitor-transfected HeLa cells, as opposed to the inhibitor control group. We also observed that circRNA THBS1-siRNA dramatically increased miR-543 expression in HeLa cells, while this promotion was abolished after miR-543 inhibitor treatment (Figure 3c). In addition, we found that compared with the control plasmid group, circRNA THBS1 plasmid significantly enhanced circRNA THBS1 expression in HeLa cells (Figure 3d), while miR-543 expression significantly reduced (Figure 3e). Based on these findings, we revealed that circRNA THBS1 negatively regulated miR-543 levels in cervical cancer cells.

Figure 3 miR-543 inhibitor abolished the effects of circRNA THBS1 on miR-543 level in HeLa cells. (a) RT-qPCR analysis of circRNA THBS1 in control-siRNA or circRNA THBS1-siRNA-transfected HeLa cells. (b) mRNA levels of miR-543 in HeLa cells were detected by RT-qPCR. (c) miR-543 levels in control-siRNA + miR-543 inhibitor- or circRNA THBS1-siRNA + miR-543 inhibitor-transfected cells. (d) RT-qPCR analysis of circRNA THBS1 in control plasmid- or circRNA THBS1 plasmid-transfected HeLa cells. (e) RT-qPCR analysis of miR-543 in control plasmid- or circRNA THBS1 plasmid-transfected HeLa cells. **P < 0.01 vs control-siRNA; ## P < 0.01 vs inhibitor control; && P < 0.01 vs circRNA THBS1-siRNA + inhibitor control.
Figure 3

miR-543 inhibitor abolished the effects of circRNA THBS1 on miR-543 level in HeLa cells. (a) RT-qPCR analysis of circRNA THBS1 in control-siRNA or circRNA THBS1-siRNA-transfected HeLa cells. (b) mRNA levels of miR-543 in HeLa cells were detected by RT-qPCR. (c) miR-543 levels in control-siRNA + miR-543 inhibitor- or circRNA THBS1-siRNA + miR-543 inhibitor-transfected cells. (d) RT-qPCR analysis of circRNA THBS1 in control plasmid- or circRNA THBS1 plasmid-transfected HeLa cells. (e) RT-qPCR analysis of miR-543 in control plasmid- or circRNA THBS1 plasmid-transfected HeLa cells. **P < 0.01 vs control-siRNA; ## P < 0.01 vs inhibitor control; && P < 0.01 vs circRNA THBS1-siRNA + inhibitor control.

3.4 Inhibition of miR-543 reversed the influence of circRNA THBS1-siRNA on HeLa cells viability, apoptosis, and EMT

To better understand the functions of circRNA THBS1 or miR-543 in HeLa cells, HeLa cells were transfected with control-siRNA, circRNA THBS1-siRNA, circRNA THBS1-siRNA + inhibitor control, or circRNA THBS1-siRNA + miR-543 inhibitor for 48 h. Results from MTT and FCM assay demonstrated that circRNA THBS1-siRNA reduced HeLa cells’ viability (Figure 4a) and promoted more apoptotic cells (Figure 4b and c). Besides, our data revealed that circRNA THBS1-siRNA inhibited the EMT of cervical cancer cells, as confirmed by enhanced E-cadherin expression (Figure 4d and e) and suppressed N-cadherin level (Figure 4d–f). However, all these findings were reversed by miR-543 inhibitor co-transfection, suggesting that circRNA THBS1 was involved in the HeLa cells’ viability, apoptosis, and EMT by sponging to miR-543.

Figure 4 circRNA THBS1-siRNA suppressed HeLa cells’ viability, promoted cells’ apoptosis, and inhibited EMT by sponging to miR-543. (a) Cells’ viability and (b) cell apoptosis were determined by MTT and FCM analyses. (c) Quantification of apoptotic cells. (d) Western blot analysis of E-cadherin and N-cadherin expressions. mRNA levels of E-cadherin (e) and N-cadherin (f) were checked using RT-qPCR. **P < 0.01 vs control-siRNA; ## P < 0.01 vs circRNA THBS1-siRNA + inhibitor control.
Figure 4

circRNA THBS1-siRNA suppressed HeLa cells’ viability, promoted cells’ apoptosis, and inhibited EMT by sponging to miR-543. (a) Cells’ viability and (b) cell apoptosis were determined by MTT and FCM analyses. (c) Quantification of apoptotic cells. (d) Western blot analysis of E-cadherin and N-cadherin expressions. mRNA levels of E-cadherin (e) and N-cadherin (f) were checked using RT-qPCR. **P < 0.01 vs control-siRNA; ## P < 0.01 vs circRNA THBS1-siRNA + inhibitor control.

3.5 miR-543 directly targets HMGB2

Having illustrated the correlation between circRNA THBS1 and miR-543, we further investigated the potential mechanisms of miR-543 in HeLa cells. According to bioinformatics tools (starBase), HMGB2 was a candidate target of miR-543 (Figure 5a). In addition, dual luciferase reporter gene system further suggested that HMGB2 was a direct target of miR-543 (Figure 5b). The dual luciferase reporter assay was also conducted in HeLa cells, and similar results were obtained (Figure A1b). All these observations above indicated that HMGB2 was a direct target of miR-543.

Figure 5 HMGB2 was a direct target of miR-543. (a) A schematic of miR-543 binding site in HMGB2 3′-UTR. (b) Dual-luciferase reporter assay system was applied for verifying the relationship between HMGB2 and miR-543. **P < 0.01 vs mimic control.
Figure 5

HMGB2 was a direct target of miR-543. (a) A schematic of miR-543 binding site in HMGB2 3′-UTR. (b) Dual-luciferase reporter assay system was applied for verifying the relationship between HMGB2 and miR-543. **P < 0.01 vs mimic control.

3.6 miR-543 negatively regulated HMGB2 expression in HeLa cells

We also illustrated the relationship between miR-543 and HMGB2 in HeLa cells, and HeLa cells were transfected with mimic control, miR-543 mimic, control plasmid, or HMGB2 plasmid for 48 h. Results from Figure 6a revealed that HMGB2 was markedly upregulated in HMGB2 plasmid-transfected cells, in comparison to the control plasmid group. Moreover, miR-543 mimic significantly reduced HMGB2 level in HeLa cells, while this inhibition was reversed after HMGB2 plasmid treatment (Figure 6b and c). According to these observations, we verified that miR-543 negatively regulated HMGB2 expression in HeLa cells.

Figure 6 HMGB2 plasmid abolished the effects of miR-543 mimic HMGB2 level. (a) RT-qPCR analysis of HMGB2 in HeLa cells after HMGB2 plasmid or control plasmid transfection. (b) mRNA levels of HMGB2 in mimic control + HMGB2 plasmid- or miR-543 mimic + HMGB2 plasmid-transfected cells. (c) protein levels of HMGB2 in mimic control + HMGB2 plasmid- or miR-543 mimic + HMGB2 plasmid-transfected cells. **P < 0.01 vs mimic control; ## P < 0.01 vs control plasmid; && P < 0.01 vs miR-543 mimic + control plasmid.
Figure 6

HMGB2 plasmid abolished the effects of miR-543 mimic HMGB2 level. (a) RT-qPCR analysis of HMGB2 in HeLa cells after HMGB2 plasmid or control plasmid transfection. (b) mRNA levels of HMGB2 in mimic control + HMGB2 plasmid- or miR-543 mimic + HMGB2 plasmid-transfected cells. (c) protein levels of HMGB2 in mimic control + HMGB2 plasmid- or miR-543 mimic + HMGB2 plasmid-transfected cells. **P < 0.01 vs mimic control; ## P < 0.01 vs control plasmid; && P < 0.01 vs miR-543 mimic + control plasmid.

3.7 Upregulation of miR-543 inhibited HeLa cells viability, EMT, and accelerated cells apoptosis by targeting HMGB2

Finally, we explained the mechanism by which miR-543 mediated HeLa cells’ biological functions. Findings from Figure 7a and b revealed that miR-543 mimic suppressed HeLa cells’ viability and accelerated more apoptotic cells. Moreover, the expression of E-cadherin (Figure 7d and e) was increased and N-cadherin was reduced (Figure 7d and f) by miR-543 mimic, as opposed to the mimic control group. Nevertheless, all these findings were reversed by HMGB2 plasmid. The findings indicated that knockdown of circRNA THBS1 inhibited the malignant biological behavior of cervical cancer cells by miR-543/HMGB2 axis.

Figure 7 miR-543 mimic inhibited the biological behavior of cervical cancer cells via HMGB2. (a and b) Cells’ viability and apoptotic cells were checked using MTT and FCM analysis. (c) Quantitation of apoptotic cells. (d) Detection of E-cadherin and N-cadherin expression using Western blot analysis. (e and f) RT-qPCR analysis of E-cadherin and N-cadherin levels in miR-543 mimic + control plasmid- or miR-543 mimic + HMGB2 plasmid-transfected HeLa cells. **P < 0.01 vs mimic control; ## P < 0.01 vs miR-543 mimic + control plasmid.
Figure 7

miR-543 mimic inhibited the biological behavior of cervical cancer cells via HMGB2. (a and b) Cells’ viability and apoptotic cells were checked using MTT and FCM analysis. (c) Quantitation of apoptotic cells. (d) Detection of E-cadherin and N-cadherin expression using Western blot analysis. (e and f) RT-qPCR analysis of E-cadherin and N-cadherin levels in miR-543 mimic + control plasmid- or miR-543 mimic + HMGB2 plasmid-transfected HeLa cells. **P < 0.01 vs mimic control; ## P < 0.01 vs miR-543 mimic + control plasmid.

4 Discussion

The findings of the current study indicated that circRNA THBS1 was significantly upregulated and miR-543 was low-expressed in cervical cancer tissues and cell lines. circRNA THBS1 silencing inhibited cervical cancer cell proliferation and EMT and induced cell apoptosis via the regulation of miR-543/HMGB2 axis, suggesting its carcinogenic role in cervical cancer.

Cervical cancer, one of the most frequent malignant tumors in women, has become the main health problem for women due to its high morbidity and mortality [15,16]. At present, radical hysterectomy [17], chemoradiation [18], and immunotherapy [19] were applied for cervical cancer treatment. However, less than 20% of cervical cancer patients are eligible for surgery after diagnosis, indicating the significance of the early diagnosis of cervical cancer. Hence, increasing numbers of investigations focused on exploring new biomarkers, which may be applied for the diagnosis and treatment of cervical cancer.

circRNAs have been evidenced to be vital regulators in many diseases, including cervical cancer [20]. In addition, numerous studies have revealed that circRNAs participate in the biological behaviors of cervical cancer cells, including cell proliferation, apoptosis, and metastasis. For instance, Huang et al. evidenced that circ-ACACA promotes cervical cancer cells’ proliferation, invasion, and migration by regulating miR-582-5p/ERO1A signaling axis [21]. circRNA THBS1, a newly discovered circRNA, has been confirmed to regulate non-small-cell lung cancer cells’ functions by sponging miR-129-5p and regulating SOX4 expression [8]. Nevertheless, little is known about circRNA THBS1’s mechanism in cervical cancer development. First, we searched the underlying targets of circRNA THBS1 in cervical cancer, and the data suggested that circRNA THBS1 sponged to miR-543, suggesting a possible relationship of circRNA THBS1 and miR-543 in cervical cancer. We also evaluated the levels of circRNA THBS1 and miR-543 in cervical cancer tissues and cervical cancer cell lines, and the data indicated that circRNA THBS1 was significantly upregulated and miR-543 was downregulated in cervical cancer tissues and cervical cancer cell lines. Our data suggested that circRNA THBS1 and miR-543 were dysregulated in cervical cancer. miR-543 was found to act as oncogene or tumor suppressor in various cancers, including glioma [22], non-small-cell lung cancer [23], and colorectal cancer [13]. However, the biological functions of miR-543 in cervical cancer are largely indistinct. Thus, we speculated that circRNA THBS1 downregulation or miR-543 upregulation may prevent tumorigenesis in cervical cancer.

The etiology of cancer is highly complex, and it has several biological behaviors including cell invasion, neo-angiogenesis, EMT, and abnormal cell proliferation and apoptosis [24–26]. Besides, accumulating evidence suggests that immune cells, adhesion molecules, extracellular matrix metalloproteinase, and pro-inflammatory cytokines activate/alter microenvironment, creating the conditions for differentiation, adhesion, proliferation, and survival of cancer cells [27,28]. In this study, we explored the role of circRNA THBS1/miR-543 in HeLa cell proliferation, apoptosis, and EMT. We found that circRNA THBS1 negatively regulated miR-543 levels in cervical cancer cells. circRNA THBS1-siRNA significantly reduced HeLa cells’ viability and EMT and promoted cell apoptosis. However, all these findings were reversed by miR-543 inhibitor, suggesting that silencing of circRNA THBS1 had available proliferation and EMT inhibition, and apoptosis promotion effect in cervical cancer cells.

Evidence has verified that dysregulation of miRNAs is associated with their biological functions by targeting mRNAs in cervical cancer. Han et al. suggested that miR-99a inhibited cervical cancer cells’ proliferation and migration by targeting IGF1R [29]. We further investigated the potential mechanisms of miR-543 in HeLa cells. The findings indicated that miR-543 directly targets HMGB2, and it negatively regulated HMGB2 expression in HeLa cells. Liu et al. suggested that miR-543 inhibited cells’ growth and metastasis by targeting TRPM7 in cervical cancer [14]. Similar results were observed in our research, and the results demonstrated that miR-543 mimic significantly reduced cell viability, promoted cell apoptosis, and inhibited EMT in HeLa cells by targeting HMGB2.

5 Conclusion

Our findings strongly showed that circRNA THBS1 regulates cervical cancer cell proliferation, apoptosis, and EMT via regulating miR-543/HMGB2 axis. The findings may help to provide a prognostic biomarker and molecular therapeutic target for cervical cancer.

# Equal contributors.

  1. Funding information: This study was supported by Shanghai Mengchao Cancer Hospital Research Project (grant no. YJKT-2022-03-01).

  2. Author contributions: Rui Tian contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. Huixin Li, Songjie Ren, Shukui Li, and Run Fang contributed to the data collection and statistical analysis. Yang Liu contributed to data collection, statistical analysis, and manuscript preparation. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors declare that they have no competing interests.

  4. Data availability statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Appendix

Figure A1 Dual-luciferase reporter assay in HeLa cells. (a) To verify the binding sites between miR-543 and circRNA THBS1, dual luciferase reporter assay was performed in HeLa cells. (b) To confirm the binding sites between miR-543 and HMGB2, dual luciferase reporter assay was performed in HeLa cells. **P<0.01 vs. mimic control.
Figure A1

Dual-luciferase reporter assay in HeLa cells. (a) To verify the binding sites between miR-543 and circRNA THBS1, dual luciferase reporter assay was performed in HeLa cells. (b) To confirm the binding sites between miR-543 and HMGB2, dual luciferase reporter assay was performed in HeLa cells. **P<0.01 vs. mimic control.

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Received: 2022-10-20
Revised: 2023-04-14
Accepted: 2023-05-07
Published Online: 2023-07-14

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

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  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
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  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
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  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
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  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
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  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
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  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
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  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0709
Schlagwörter für diesen Artikel
circRNA THBS1; cervical cancer cells; miR-543/HMGB2 axis
Creative Commons
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Artikel in diesem Heft

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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Heruntergeladen am 18.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0709/html
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