Home Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
Article Open Access

Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression

  • Ling Zhang EMAIL logo , Jingtao Song , Xu Xin , Donghong Sun , Huiting Huang , Yang Chen , Tao Zhang and Yiming Zhang
Published/Copyright: July 22, 2021
Download Article (PDF)
Open Medicine
From the journal Open Medicine Volume 16 Issue 1

Abstract

Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents. This study aims to reveal that hypoxia promotes the invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. The expression of HIF-1α and NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6–36 h. Furthermore, hypoxia induced the migration and invasion of MG63 cells and regulated the level of E-cad, N-cad, Vimentin, Snail, Slug, MMP2, and MMP9 proteins. Importantly, knockdown of NUSAP1 inhibited hypoxia-induced cell migration and invasion. In the hypoxia microenvironment, the addition of HIF-1α inhibitor or the transfection of siRNA specifically targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 and markedly inhibited the migration and invasion of MG63 cells under the hypoxia microenvironment. In conclusion, hypoxia induced the expression of NUSAP1 in a HIF-1α-dependent manner, stimulating the migration and invasion of MG63 cells.

Keywords: osteosarcoma; hypoxia; HIF-1α; NUSAP1; migration; invasion

1 Introduction

Osteosarcoma is a highly aggressive malignant tumor, which most commonly occurs in children and adolescents [1]. The combination of neoadjuvant chemotherapy and traditional surgical resection is the main treatment strategy for osteosarcoma, which improves the overall survival of patients with local osteosarcoma [2]. However, osteosarcoma has a high recurrence rate and is prone to lung metastasis. For metastatic and recurrent osteosarcoma, the combination of surgery and chemotherapy cannot produce satisfactory outcomes [3]. In other words, the clinical outcome of patients with osteosarcoma has not improved significantly. This stagnation of therapeutic advances may be attributed to the unclear mechanism of the osteosarcoma occurrence and metastasis [4]. Therefore, understanding the specific mechanisms of biomolecules in the occurrence and metastasis of osteosarcoma is important to improve the prognosis of patients with osteosarcoma.

Intratumoral hypoxia is a typical feature of solid tumors [5]. This is mainly due to the increase in oxygen consumption caused by the rapid growth of tumor mass and the limited blood supply caused by newly formed vascular malformations. Hypoxia is a vital component of the tumor microenvironment, which is closely related to cell proliferation, tumor invasion, angiogenesis, and distant metastasis [6,7]. The adaptation of tumor cells to hypoxia led to the selection of tumor heterogenous and resistant clones, which evolved into more aggressive phenotypes and resistance to multiple therapeutic drugs [8]. Tumor metastasis and drug resistance caused by hypoxia have also been demonstrated in osteosarcoma [9,10]. However, further understanding of hypoxia-driven metastasis mechanisms is needed.

Nucleolar and spindle-associated protein 1 (NUSAP1) can control the cell cycle progression by promoting the accumulation of microtubules [11,12,13]. The high expression of NUSAP1 has been found in a variety of tumor types and is closely related to tumor cell proliferation, apoptosis, and drug resistance [14,15,16]. However, the role of NUSAP1 in the hypoxia response of osteosarcoma has not been reported. Although, one study has found that hypoxic stress stimulates the rapid translation of NUSAP1 in pancreatic cancer cells [17].

In this study, we found that hypoxia induced the expression of NUSAP1, thereby stimulating the migration and invasion of MG63 cells. Additionally, hypoxia-induced NUSAP1 expression and MG63 cell migration and invasion are HIF-1α dependent.

2 Materials and methods

2.1 Cell lines and cell culture

The human osteosarcoma cell line MG63 was purchased from the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (Shanghai, China). Cells were maintained in Dulbecco’s Modified Eagle’s Medium (DMEM) (Gibco, Grand Island, NY) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, MA), 100 U/mL penicillin, and 100 mg/mL streptomycin. For the normoxic culture, cells were incubated at 37 °C with 5% CO2, 20% O2, and 75% N2 in a humidified incubator (Thermo Fisher Scientific, Waltham, MA). For the hypoxia culture, cells were exposed at 37°C with 1% O2, 5% CO2, and 94% N2 in a humidified incubator.

2.2 Cell transfection and treatment

MG63 cells were transfected with siRNA targeting NUSAP1 or negative control siRNA (Ruibo, Guangzhou, China) using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions. HIF-1α inhibitor (LW6) was obtained from MedChemExpress (Cat. No. HY-13671).

2.3 Transwell assay

The migration and invasion abilities of MG63 cells were detected by the Transwell assay. For cell migration, 2,000 cells maintained in 200 μL of serum-free medium were seeded in the upper well of the Transwell chamber (8 μm pore size; Corning, Shanghai, China). About 600 μL of DMEM containing 10% FBS was loaded into the lower well. After 24 h of incubation, cells that did not migrate through the pores were carefully wiped with a cotton swab. The cells located on the lower surface of the chamber were fixed with 4% paraformaldehyde for 30 min and stained with 0.1% crystal violet for 30 min at room temperature. The stained cells were counted under a light microscope (Olympus, Tokyo, Japan) from five random fields. For cell invasion, the upper chamber was coated with the Matrigel (BD Biosciences, San Jose, CA). Then, the other operations were consistent with cell migration experiments.

2.4 Western blotting

Proteins were lysed from MG63 cells with RIPA buffer containing the protease and phosphatase inhibitors and quantified using the BCA assay (Beyotime, Shanghai, China). An equal amount of protein from each sample was loaded on a 10% SDS-PAGE gel and electrophoresed. Then, the proteins were transferred to a PVDF membrane (EMD Millipore, Billerica, MA), following block with 5% fat-free milk for 1 h at room temperature. The blots were incubated with primary antibodies overnight at 4°C. After washing three times with TBST, the membrane was incubated with HRP-conjugated secondary antibodies, and the immunoblots were visualized using ECL detection kit (Thermo Fisher Scientific). Software QUANTITY ONE was used to measure the intensity of bands. β-actin was used as the reference.

The primary antibodies used in this study were as follow: anti-hypoxia-inducible factor 1α (HIF-1α) (ab1, mouse monoclonal), anti-NUSAP1 (ab169083, mouse polyclonal), anti-N-cadherin (ab18203, rabbit polyclonal), anti-Vimentin (ab8978, mouse monoclonal), anti-Snail (ab229701, rabbit monoclonal), anti-Slug (ab51772, mouse monoclonal), anti-MMP2 (ab92536, rabbit monoclonal), anti-MMP9 (ab38898, rabbit polyclonal), and anti-β-actin (ab8226, mouse monoclonal) were purchased from Abcam. Anti-E-cadherin (20874-1-AP, rabbit polyclonal) was purchased from Proteintech.

2.5 Statistical analysis

Statistical analysis was performed with GraphPad Prism 5 (GraphPad Software, La Jolla, CA). All data were expressed as means ± SEM from three or more independent experiments. The differences between the groups were determined by Student’s t-test or one-way ANOVA and considered significant at P < 0.05.

3 Results

3.1 Hypoxia induces NUSAP1 expression in MG63 cells

We investigated the effects of hypoxia on the expression of NUSAP1 in human osteosarcoma cell line MG63. As shown in Figure 1a, the expression of NUSAP1 was significantly up-regulated in MG63 cells cultured in hypoxia for 6–36 h. In addition, the level of HIF-1α increased significantly under the hypoxia microenvironment for 6–36 h.

Figure 1 Hypoxia induces NUSAP1 expression and stimulates the migration and invasion of MG63 cells. (a) The expression of HIF-1α and NUSAP1 in MG63 cells cultured with hypoxia for 0, 6, 12, 24, and 36 h was detected using western blot. (b) The migration and invasion of MG63 cells cultured with normoxia or hypoxia for 24 h was measured using transwell assay. (c) The expression of EMT-related proteins in MG63 cells cultured with normoxia or hypoxia for 48 h was detected using western blot. (d) The expression of MMP family membranes in MG63 cells cultured with normoxia or hypoxia for 48 h was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group.
Figure 1

Hypoxia induces NUSAP1 expression and stimulates the migration and invasion of MG63 cells. (a) The expression of HIF-1α and NUSAP1 in MG63 cells cultured with hypoxia for 0, 6, 12, 24, and 36 h was detected using western blot. (b) The migration and invasion of MG63 cells cultured with normoxia or hypoxia for 24 h was measured using transwell assay. (c) The expression of EMT-related proteins in MG63 cells cultured with normoxia or hypoxia for 48 h was detected using western blot. (d) The expression of MMP family membranes in MG63 cells cultured with normoxia or hypoxia for 48 h was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group.

3.2 Hypoxia stimulates MG63 cell migration and invasion

Subsequently, the effect of hypoxia on the migration and invasion of MG63 cells was measured by the Transwell assay. As shown in Figure 1b, the number of migrating and invading cells increased after exposure to hypoxia (P < 0.05). Furthermore, the hypoxia microenvironment regulated the expression of EMT-related proteins. As shown in Figure 1c, the hypoxia microenvironment down-regulated the expression of E-cad of MG63 cells, while up-regulating the level of N-cad, Vimentin, Snail, and Slug (P < 0.05). We also found that the expression of MMP2 and MMP9 significantly increased under the hypoxia microenvironment (Figure 1d, P < 0.05).

3.3 Knockdown of NUSAP1 represses the migration and invasion of MG63 cells

To investigate whether hypoxia-induced cell migration and invasion are related to the hypoxia-induced high expression of NUSAP1, NUSAP1 expression was knocked down by transfection of siRNA-NUSAP1 under hypoxia condition. As shown in Figure 2a, after knocking down the NUSAP1 expression, the number of migrating and invading cells under hypoxia conditions was markedly reduced. Knockdown of NUSAP1 significantly suppressed the expression of N-cad, Vimentin, Snail, Slug, MMP2, and MMP9, while it markedly promoted the expression of E-cad (Figure 2b and c, P < 0.05).

Figure 2 Knockdown of NUSAP1 represses the migration and invasion of MG63 cells under hypoxia. (a) The migration and invasion of MG63 cells whose NUSAP1 expression was knocked down (Hypoxia + KD) under hypoxia condition was measured using transwell assay. (b) The expression of EMT-related proteins was detected using western blot. (c) The expression of MMP family membranes was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group; # P < 0.05, compared with Hypoxia group.
Figure 2

Knockdown of NUSAP1 represses the migration and invasion of MG63 cells under hypoxia. (a) The migration and invasion of MG63 cells whose NUSAP1 expression was knocked down (Hypoxia + KD) under hypoxia condition was measured using transwell assay. (b) The expression of EMT-related proteins was detected using western blot. (c) The expression of MMP family membranes was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group; # P < 0.05, compared with Hypoxia group.

In addition, we also measured the effect of down-regulation of NUSAP1 expression on MG63 cell migration and invasion under normoxia. As shown in Figure 3, knockdown of NUSAP1 inhibited cell migration and invasion and regulated the expression of EMT-related proteins and MMP proteins.

Figure 3 Knockdown of NUSAP1 represses the migration and invasion of MG63 cells. (a) The migration and invasion of MG63 cells whose NUSAP1 expression was knocked down (NUSAP1-KD) under normoxia condition was measured using transwell assay. (b) The expression of EMT-related proteins was detected using western blot. (c) The expression of MMP family membranes was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with NC group.
Figure 3

Knockdown of NUSAP1 represses the migration and invasion of MG63 cells. (a) The migration and invasion of MG63 cells whose NUSAP1 expression was knocked down (NUSAP1-KD) under normoxia condition was measured using transwell assay. (b) The expression of EMT-related proteins was detected using western blot. (c) The expression of MMP family membranes was detected using western blot. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with NC group.

3.4 Hypoxia increases NUSAP1 expression and MG63 cell migration and invasion is HIF-1α dependent

HIF-1α is the central transcription factor that regulates the transcription of hypoxia-responsive genes and the adaptive response of cells to hypoxia. Therefore, we further evaluated whether the hypoxia-induced up-regulation of NUASP1 expression is HIF-1α dependent. In the hypoxia microenvironment, the addition of HIF-1α inhibitor (Figure 4a) and the transfection of siRNA specifically targeting HIF-1α (siHIF-1α) (Figure 4c) can significantly reduce the expression of HIF-1α and NUSAP1 (P < 0.05). Additionally, the addition of HIF-1α inhibitor and the transfection of siHIF-1α both markedly inhibited the cell migration and invasion under the hypoxia microenvironment (Figure 4b and d, P < 0.05).

Figure 4 Hypoxia increases NUSAP1 expression and MG63 cell migration and invasion is HIF-1α dependent. The expression of HIF-1α and NUSAP1 in MG63 cells incubated with HIF-1α inhibitor (Hypoxia + In) (a) or siRNA targeting HIF-1α (siHIF-1α) (c) under hypoxia condition was detected using western blot. The migration and invasion of MG63 cells incubated with HIF-1α inhibitor (b) or siRNA targeting HIF-1α (siHIF-1α) (d) under hypoxia condition was measured using transwell assay. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group; # P < 0.05, compared with Hypoxia group.
Figure 4

Hypoxia increases NUSAP1 expression and MG63 cell migration and invasion is HIF-1α dependent. The expression of HIF-1α and NUSAP1 in MG63 cells incubated with HIF-1α inhibitor (Hypoxia + In) (a) or siRNA targeting HIF-1α (siHIF-1α) (c) under hypoxia condition was detected using western blot. The migration and invasion of MG63 cells incubated with HIF-1α inhibitor (b) or siRNA targeting HIF-1α (siHIF-1α) (d) under hypoxia condition was measured using transwell assay. All experiments were independently carried out in three replicates. *P < 0.05, **P < 0.01, ***P < 0.001, compared with normoxia group; # P < 0.05, compared with Hypoxia group.

4 Discussion

Osteosarcoma is a common primary malignant tumor, accounting for more than 10% of solid cancers in children and adolescents [18]. Although the treatment of osteosarcoma has made great progress in the past 20 years, the overall survival rate of osteosarcoma patients has not improved due to metastasis and recurrence [19]. Therefore, it is necessary to understand its underlying biological reasons to improve the outcome of osteosarcoma treatment. In this study, we found that hypoxia can promote the migration and invasion of osteosarcoma cells by up-regulating the expression of NUSAP1. These findings may provide a valuable target for the treatment of osteosarcoma.

Hypoxia is an important prognostic and driven factor for many types of tumors [20,21]. In this study, we found that hypoxia induced the expression of NUSAP1. Furthermore, one study has shown that hypoxia stimulates the rapid translation of NUSAP1 in pancreatic cancer cells [17]. Additionally, we also found that hypoxia promoted the migration and invasion of osteosarcoma cells and regulated the expression of EMT- and MMP-related proteins. Hypoxia-induced cell migration and invasion were related to the high expression of NUSAP1 induced by hypoxia. After knocking down the expression of NUSAP1, the number of migrating and invading cells under hypoxia was markedly reduced.

The members of the HIF family are oxygen sensors that mediate the response of mammalian cells to hypoxia [22]. The members of this family contain an oxygen-sensitive HIF-α subunit and a constitutively expressed HIF-β subunit [22]. HIF-1α is widely used as a marker of poor prognosis in cancer patients. It can act as a signaling center, transcriptionally regulating the expression of many transcription factors and signaling molecules that play a key role in tumorigenesis [22]. Additionally, HIF-1α plays an important role in the response of cells to hypoxia by inducing glycolysis and angiogenesis [23]. Some studies have also shown that HIF-1a is up-regulated in osteosarcoma and is associated with the metastasis and poor prognosis [5,24,25]. In this study, we found that the increased NUSAP1 expression and MG63 cell migration and invasion induced by hypoxia were HIF-1α dependent. The results of the western blot showed that the addition of HIF-1α inhibitor or the transfection of siRNA targeting HIF-1α significantly reduced the expression of HIF-1α and NUSAP1 in the hypoxia microenvironment and markedly inhibited the cell migration and invasion. We speculated that NUSAP1 was the downstream target of HIF-1α transcriptional regulation and participates in the regulation of osteosarcoma cell migration and invasion in a HIF-1α-dependent manner.

We reported for the first time the role of NUSAP1 in osteosarcoma, which is consistent with its role in other types of tumors. NUSAP1 plays an oncogene role in tumors, which is mainly involved in regulating tumor cell proliferation and apoptosis [14,15,16]. This study also demonstrates the link between NUSAP1 and tumor cell migration and invasion.

In conclusion, hypoxia induced the NUSAP1 expression in a HIF-1α-dependent manner in MG63 cells, which stimulated the migration and invasion. HIF-1α and NUSAP1 were valuable targets for the treatment of osteosarcoma.

tel: +86-13582762585

Acknowledgments

The authors declare that they have no competing interests, and all authors should confirm its accuracy.

  1. Funding information: The authors received no financial support for the research, authorship and/or publication of this article.

  2. Conflict of interest: Authors state no conflict of interest.

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

References

[1] Kager L, Tamamyan G, Bielack S. Novel insights and therapeutic interventions for pediatric osteosarcoma. Future Oncol. 2017;13(4):357–68.10.2217/fon-2016-0261Search in Google Scholar PubMed

[2] Simpson S, Dunning MD, de Brot S, Grau-Roma L, Mongan NP, Rutland CS. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics. Acta Vet Scand. 2017;59(1):71.10.1186/s13028-017-0341-9Search in Google Scholar PubMed PubMed Central

[3] Anderson ME. Update on survival in osteosarcoma. Orthop Clin North Am. 2016;47(1):283–92.10.1016/j.ocl.2015.08.022Search in Google Scholar PubMed

[4] Morrow JJ, Khanna C. Osteosarcoma genetics and epigenetics: emerging biology and candidate therapies. Crit Rev Oncog. 2015;20(3–4):173–97.10.1615/CritRevOncog.2015013713Search in Google Scholar PubMed PubMed Central

[5] Zhang B, Li YL, Zhao JL, Zhen O, Yu C, Yang BH, et al. Hypoxia-inducible factor-1 promotes cancer progression through activating AKT/Cyclin D1 signaling pathway in osteosarcoma. Biomed Pharmacother. 2018;105:1–9.10.1016/j.biopha.2018.03.165Search in Google Scholar PubMed

[6] Sun Y, Wang H, Liu M, Lin F, Hua J. Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1alpha protein. Mol Med Rep. 2015;11(3):1975–81.10.3892/mmr.2014.2913Search in Google Scholar PubMed

[7] Chang J, Erler J. Hypoxia-mediated metastasis. Adv Exp Med Biol. 2014;772:55–81.10.1007/978-1-4614-5915-6_3Search in Google Scholar PubMed

[8] Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–32.10.1038/nrc1187Search in Google Scholar PubMed

[9] Zhao C, Zhang Q, Yu T, Sun S, Wang W, Liu G. Hypoxia promotes drug resistance in osteosarcoma cells via activating AMP-activated protein kinase (AMPK) signaling. J Bone Oncol. 2016;5(1):22–9.10.1016/j.jbo.2016.01.002Search in Google Scholar PubMed PubMed Central

[10] Cao J, Wang Y, Dong R, Lin G, Zhang N, Wang J, et al. Hypoxia-induced WSB1 promotes the metastatic potential of osteosarcoma cells. Cancer Res. 2015;75(22):4839–51.10.1158/0008-5472.CAN-15-0711Search in Google Scholar PubMed

[11] Li C, Zhang Y, Yang Q, Ye F, Sun SY, Chen ES, et al. NuSAP modulates the dynamics of kinetochore microtubules by attenuating MCAK depolymerisation activity. Sci Rep. 2016;6:18773.10.1038/srep18773Search in Google Scholar PubMed PubMed Central

[12] Li C, Xue C, Yang Q, Low BC, Liou YC. NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force. Nat Commun. 2016;7:10597.10.1038/ncomms10597Search in Google Scholar PubMed PubMed Central

[13] Vanden Bosch A, Raemaekers T, Denayer S, Torrekens S, Smets N, Moermans K, et al. NuSAP is essential for chromatin-induced spindle formation during early embryogenesis. J Cell Sci. 2010;123(Pt 19):3244–55.10.1242/jcs.063875Search in Google Scholar PubMed

[14] Zhang X, Pan Y, Fu H, Zhang J. Nucleolar and spindle associated protein 1 (NUSAP1) inhibits cell proliferation and enhances susceptibility to epirubicin in invasive breast cancer cells by regulating cyclin D kinase (CDK1) and DLGAP5 expression. Med Sci Monit. 2018;24:8553–64. 10.12659/MSM.910364Search in Google Scholar PubMed PubMed Central

[15] Gordon CA, Gong X, Ganesh D, Brooks JD. NUSAP1 promotes invasion and metastasis of prostate cancer. Oncotarget. 2017;8(18):29935–50.10.18632/oncotarget.15604Search in Google Scholar PubMed PubMed Central

[16] Zhu T, Xie P, Gao YF, Huang MS, Li X, Zhang W, et al. Nucleolar and spindle-associated protein 1 is a tumor grade correlated prognosis marker for glioma patients. CNS Neurosci Ther. 2018;24(3):178–86.10.1111/cns.12803Search in Google Scholar PubMed PubMed Central

[17] Gupta N, Park JE, Tse W, Low JK, Kon OL, McCarthy N, et al. ERO1alpha promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer. Oncotarget. 2019;10(57):5970–82.10.18632/oncotarget.27235Search in Google Scholar PubMed PubMed Central

[18] Bielack S, Carrle D, Casali PG, Group EGW. Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):137–9.10.1093/annonc/mdp154Search in Google Scholar PubMed

[19] Meazza C, Scanagatta P. Metastatic osteosarcoma: a challenging multidisciplinary treatment. Expert Rev Anticancer Ther. 2016;16(5):543–56.10.1586/14737140.2016.1168697Search in Google Scholar PubMed

[20] Petrova V, Annicchiarico-Petruzzelli M, Melino G, Amelio I. The hypoxic tumour microenvironment. Oncogenesis. 2018;7(1):10.10.1038/s41389-017-0011-9Search in Google Scholar PubMed PubMed Central

[21] Rankin EB, Giaccia AJ. Hypoxic control of metastasis. Science. 2016;352(6282):175–80.10.1126/science.aaf4405Search in Google Scholar PubMed PubMed Central

[22] Manoochehri Khoshinani H, Afshar S, Najafi R. Hypoxia: a double-edged sword in cancer therapy. Cancer Invest. 2016;34(10):536–45.10.1080/07357907.2016.1245317Search in Google Scholar PubMed

[23] Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA. 1997;94(15):8104–9.10.1073/pnas.94.15.8104Search in Google Scholar PubMed PubMed Central

[24] Ren HY, Zhang YH, Li HY, Xie T, Sun LL, Zhu T, et al. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis. Onco Targets Ther. 2016;9:1477–87.10.2147/OTT.S95490Search in Google Scholar PubMed PubMed Central

[25] Zhao H, Wu Y, Chen Y, Liu H. Clinical significance of hypoxia-inducible factor 1 and VEGF-A in osteosarcoma. Int J Clin Oncol. 2015;20(6):1233–43.10.1007/s10147-015-0848-xSearch in Google Scholar PubMed

Received: 2020-05-08
Revised: 2021-03-17
Accepted: 2021-05-23
Published Online: 2021-07-22

© 2021 Ling Zhang et al., published by De Gruyter

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

Articles in the same Issue

  1. Research Articles
  2. Identification of ZG16B as a prognostic biomarker in breast cancer
  3. Behçet’s disease with latent Mycobacterium tuberculosis infection
  4. Erratum
  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
  6. Research Articles
  7. GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
  11. SLC12A8 plays a key role in bladder cancer progression and EMT
  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
https://doi.org/10.1515/med-2020-0180
Keywords for this article
osteosarcoma; hypoxia; HIF-1α; NUSAP1; migration; invasion
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Identification of ZG16B as a prognostic biomarker in breast cancer
  3. Behçet’s disease with latent Mycobacterium tuberculosis infection
  4. Erratum
  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
  6. Research Articles
  7. GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
  11. SLC12A8 plays a key role in bladder cancer progression and EMT
  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/med-2020-0180/html
Scroll to top button