Startseite LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
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LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme

  • Ming Lei , Xinghua Du , Xiaokai Li , Fuke Wang , Ling Gu EMAIL logo und Feng Guo EMAIL logo
Veröffentlicht/Copyright: 11. Februar 2022
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Aus der Zeitschrift Open Life Sciences Band 17 Heft 1

Abstract

This study aimed to reveal the mechanism by which long noncoding RNAs (lncRNAs) modulate hepatocellular carcinoma (HCC) by regulating mRNA via the N6-methyladenosine (m6A) enzyme. The expression and clinical data of 365 HCC patients and 50 healthy control samples were downloaded from the the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) screened using limma packages from the R. m6A2Target database were used to predict the relationship between m6A enzyme-lncRNA and m6A enzyme-mRNA. The mRNAs in the lncRNA-m6A enzyme-mRNA network were subjected to enrichment analysis. Cox regression analysis was used to screen for RNAs significantly related to HCC prognosis. The expression of differentially expressed RNAs (DERs) was verified using the TCGA dataset and GSE55092. Eighty-five DElncRNAs and 747 DEmRNAs were identified. The mRNAs in the lncRNA-m6A enzyme-mRNA network were primarily involved in mitotic cell division, the p53 signaling pathway, and the cell cycle. Three lncRNAs and 14 mRNAs were significantly associated with HCC prognosis. Furthermore, the expression of 12 DERs differed significantly between patients in the early and advanced stages. LINC00665 was predicted to regulate 11 mRNAs by modulating IGF2BP1, IGF2BP2, and YTHDF1. Thus, this study provides new insights into the roles of lncRNA and m6A enzymes in HCC.

Keywords: hepatocellular carcinoma; N6-methyladenosine; long noncoding RNA; prognosis; comprehensive network

1 Introduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide [1]. HCC usually occurs in the context of chronic liver disease, and its occurrence is related to complex interactions among the host, the disease, and environmental factors. Among them, chronic hepatitis B or C virus infection is the primary risk factor for HCC worldwide [2]. Histological examination of the liver has consistently been used as the gold standard for the diagnosis of HCC. However, the risk of bleeding and tumor cell proliferation during biopsy is an ongoing problem during diagnosis [3]. Statistically, the 5-year survival rate of primary liver cancer in the United States is approximately 16% [4], which is close to that in Europe [5], whereas the survival rate of HCC in underdeveloped areas may be less than 5%. Thus, there is considerable research being undertaken currently on understanding the molecular genetic mechanism underlying HCC to provide a theoretical basis for the diagnosis and treatment of HCC.

N6-methyladenosine (m6A) accounts for approximately 50% of ribonucleotides in mammals [6]. Similar to DNA methylation, epigenetic regulation of m6A modulation is reversible in mammalian cells. The m6A enzymes include “writers,” “erasers,” and “readers,” which can add, remove, or recognize m6A-modified sites, respectively, to alter important biological processes [7]. M6A methylation affects RNA expression, shearing, and translation. Various studies have found that m6A methylation plays a critical role in tumor progression [8]. In addition, abnormal m6A modifications are closely associated with cancer. Researchers have observed that the methylation of m6A RNA is associated with the self-renewal of glioblastoma stem cells (GSCs), and the presence of GSCs indicates a poor prognosis for glioblastoma multiforme [9]. The m6A methylation enzyme, methyltransferase-like 3 (METTL3), participates in maintaining pluripotency and inhibiting cell differentiation in acute myeloid leukemia by mediating the elevation of m6A [10]. Abnormal upregulation of METTL3 has been identified in patients with HCC, and it often involves the progression of HCC.

Long noncoding RNAs (lncRNAs) are functionally diverse species of noncoding RNA. Studies have demonstrated that lncRNA expression may be closely related to cancer development [11,12]. Several studies have elucidated the regulatory effects of lncRNAs on HCC. Wang et al. reported that lncRNA MCM3AP-AS1 promotes the growth of HCC cells [13], whereas Chen et al. identified that lncRNA CDKN2BAS could predict poor prognosis in patients with HCC and promote metastasis [14]. However, few studies have delineated the exact mechanism by which lncRNAs regulate mRNA expression by modulating m6A regulatory factors.

Based on The Cancer Genome Atlas (TCGA), RNA-seq expression dataset, and m6A enzyme-targeting gene database, this study aimed to reveal how lncRNAs play a role in HCC by regulating m6A regulators to further influence mRNA (Figure S1).

2 Materials and methods

2.1 Data collection and preprocessing

HCC gene expression data were downloaded from the TACG database (https://gdc-portal.nci.nih.gov/) on April 28, 2021. A total of 423 samples were included, comprising 365 tumor samples with clinical information and 50 healthy control samples. The detected lncRNAs and mRNAs were annotated according to the annotation information of the detection platform (Illumina HiSeq 2000 RNA Sequencing, Illumina, Inc., San Diego, California).

2.2 Screening of differentially expressed RNAs (DERs)

Samples were divided into tumor and control groups based on the sample information. DERs between the tumor and control groups were screened using the limma package (version 3.347, Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia) of R3.6.1 [15] with a false discovery rate (FDR) of <0.05, and |log 2 fold change| >1 as the threshold for significance. Subsequently, a bidirectional hierarchical clustering based on the centered Pearson correlation algorithm using R3.6.1 pheatmap version 1.2.8 [16] was performed on the expression values of DERs.

2.3 Comprehensive network construction and enrichment analysis

First, the m6A2Target database [17] was used to predict the lncRNAs and mRNAs related to the m6A enzyme. Second, the m6A-related lncRNAs and mRNAs intersected with the significant DERs screened in the previous step. Subsequently, these intersected DERs were selected to construct the differentially expressed lncRNAs (DElncRNAs)-m6A enzyme and differentially expressed mRNAs (DEmRNAs)-m6A enzyme network. After that, the Pearson correlation coefficient (PCC) between the expression levels of significant DElncRNAs and DEmRNAs related to the m6A enzyme was calculated. The DElncRNAs–DEmRNAs coexpression network was constructed with p <0.05 and |PCC| >0.5. Furthermore, the lncRNAs-m6A enzyme-mRNAs comprehensive network was constructed by combining the DElncRNAs-m6A enzyme and DEmRNAs-m6A enzyme network. All the networks constructed in this study were visualized using Cytoscape (version 3.6.1, National Institute of General Medical Sciences, USA) software (http://www.cytoscape.org/).

Finally, significant DEmRNAs in the comprehensive network underwent gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using DAVID (version 6.8, Laboratory of Human Retrovirology and Immunoinformatic, USA) [18,19]. Terms with more than two genes enriched and FDR <0.05 were considered to be significantly enriched terms.

2.4 Prognostic correlation analysis of lncRNAs and mRNAs in the comprehensive network

Univariate and multivariate Cox regression analyses in the survival package (version 2.41-1) [20] of R3.6.1 were used to screen for significantly independent prognostic lncRNAs and mRNAs. Based on the median expression level of target lncRNAs and mRNAs, the samples were divided into groups with a high expression level (expression level above or equal to the median expression level) and low expression level (expression level below the median expression level). The Kaplan–Meier (K–M) curve was used to evaluate the association between target lncRNAs and mRNA expression levels as well as prognosis.

2.5 Expression level analysis of lncRNAs and mRNAs in the comprehensive network in different clinical groups

Independent prognostic clinical factors were screened using univariate and multivariate Cox regression analyses in the survival package (version 2.41-1) of R3.6.1. A log-rank p value less than 0.05 was selected as the threshold for screening independent prognostic clinical factors.

Based on the screened independent prognostic clinical factor information, the samples were divided into different clinical factor feature groups, and the variations in the expression levels of the DERs screened in the previous step were analyzed using the between groups t-test in R3.6.1.

2.6 Verification of the expression of DERs

The expression values of RNAs with significantly different expression levels in different independent prognostic clinical factors screened in the previous step were extracted from the TCGA dataset to analyze the expression differences of these RNAs between tumor samples and normal samples. GSE55092 was subsequently downloaded from the National Center for Biotechnology Information Search database Gene Expression Omnibus database to analyze the expression of DERs. A total of 49 HCC tumor samples and 91 control samples were included in the GSE55092.

3 Results

3.1 Screening of DERs

After annotation, 1,241 lncRNAs and 14,164 mRNAs were identified. A total of 85 DElncRNAs and 747 DEmRNAs were screened between the tumor and control groups (Figure 1a). Thereafter, the upregulated and downregulated top 50 DERs were selected for bidirectional hierarchical clustering according to the ascending power of their log FC values. The heat map obtained has been depicted in Figure 1b, wherein it can be noted that the samples were aggregated in two different directions.

Figure 1 DElncRNAs and DEmRNAs (DERs): (a) the volcano plot of DERs and (b) two-way hierarchical clustering heat map of top50 expression levels of DERs. Red and cyan dots indicate significant differences between upregulated and downregulated expressed DERs, respectively.
Figure 1

DElncRNAs and DEmRNAs (DERs): (a) the volcano plot of DERs and (b) two-way hierarchical clustering heat map of top50 expression levels of DERs. Red and cyan dots indicate significant differences between upregulated and downregulated expressed DERs, respectively.

3.2 Comprehensive network construction

m6A enzyme-related lncRNAs were intersected with DElncRNAs, following which 53 DElncRNAs related to m6A enzyme and 12 m6A enzyme enzymes were identified (Figure 2a). This network included 162 connection pairs. Furthermore, a DEmRNAs-m6A enzyme network was also constructed, comprising 127 m6A enzyme-related DEmRNAs and 14 m6A enzyme enzymes (Figure 2b). Subsequently, the lncRNA-mRNA coexpression network containing 53 DElncRNAs and 127 DEmRNAs was created (Figure 2c). There were 945 significantly correlated connection pairs identified in this coexpression network.

Figure 2 (a) lncRNA-m6A protein network, (b) mRNA-m6A enzyme network, (c) mRNA-lncRNA network, and (d) lncRNA-m6A enzyme-mRNA comprehensive network.
Figure 2

(a) lncRNA-m6A protein network, (b) mRNA-m6A enzyme network, (c) mRNA-lncRNA network, and (d) lncRNA-m6A enzyme-mRNA comprehensive network.

In conjunction with the results of the above analysis, a DElncRNAs-m6A enzyme-DEmRNAs network was constructed (Figure 2d). Moreover, the enrichment analysis of GO and KEGG signaling pathways was performed on the DEmRNAs that constituted the DElncRNAs-m6A enzyme-DEmRNAs network. A total of 16 significant GO biological processes and 7 KEGG signaling pathways were screened (Table 1). Enriched biological processes primarily included cell division, proliferation, and mitotic division. Similarly, the KEGG pathways are generally involved in transcriptional misregulation in cancer, the FoxO signaling pathway, the p53 signaling pathway, and cell cycle.

Table 1

GO biological process and KEGG signal pathways in which mRNAs in the comprehensive network are significantly related

Category Term Count p Value FDR
Biology process GO:0007062∼sister chromatid cohesion 12 3.35 × 10−11 1.40 × 10−8
GO:0051301∼cell division 18 4.06 × 10−11 1.40 × 10−8
GO:0007067∼mitotic nuclear division 15 3.49 × 10−10 8.02 × 10−8
GO:0006260∼DNA replication 10 4.62 × 10−7 7.97 × 10−5
GO:0008283∼cell proliferation 13 2.47 × 10−6 3.41 × 10−4
GO:0006334∼nucleosome assembly 8 8.49 × 10−6 8.37 × 10−4
GO:0000086∼G2/M transition of mitotic cell cycle 8 2.13 × 10−5 1.84 × 10−3
GO:0000082∼G1/S transition of mitotic cell cycle 7 3.85 × 10−5 2.95 × 10−3
GO:0031145∼anaphase-promoting complex-dependent catabolic process 6 1.24 × 10−4 8.54 × 10−3
GO:0031577∼spindle checkpoint 3 2.22 × 10−4 1.39 × 10−2
GO:0000070∼mitotic sister chromatid segregation 4 4.67 × 10−4 2.48 × 10−2
GO:0031536∼positive regulation of exit from mitosis 3 5.50 × 10−4 2.71 × 10−2
GO:0007093∼mitotic cell cycle checkpoint 4 9.77 × 10−4 4.29 × 10−2
GO:0051726∼regulation of cell cycle 6 9.95 × 10−4 4.29 × 10−2
GO:1904668∼positive regulation of ubiquitin protein ligase activity 3 1.30 × 10−3 4.74 × 10−2
GO:0030071∼regulation of mitotic metaphase/anaphase transition 3 1.30 × 10−3 4.74 × 10−2
KEGG pathway hsa04110:Cell cycle 13 3.42 × 10−14 2.77 × 10−12
hsa04114:Oocyte meiosis 7 1.35 × 10−7 1.09 × 10−5
hsa04914:Progesterone-mediated oocyte maturation 6 3.97 × 10−7 3.22 × 10−5
hsa04115:p53 signaling pathway 3 9.78 × 10−5 7.92 × 10−3
hsa04068:FoxO signaling pathway 3 2.96 × 10−4 2.40 × 10−2
hsa05202:Transcriptional misregulation in cancer 3 4.02 × 10−4 3.26 × 10−2
hsa04974:Protein digestion and absorption 2 5.71 × 10−4 4.62 × 10−2

3.3 Prognostic correlation analysis

From the DElncRNAs and DEmRNAs included in the comprehensive network – along with clinical prognosis information of TCGA samples – univariate Cox regression analysis was used to screen the DERs significantly associated with survival prognosis. A total of 83 DERs significantly associated with prognosis were screened, including 7 lncRNAs and 76 mRNAs (Table S1). Multivariate Cox regression analysis was subsequently performed on these 83 DERs for independent prognostic-related DERs. Finally, 17 significantly independent prognosis-related DERs were obtained (Table 2). Patients were divided into two groups according to the median expression level of the 17 DERs. The K–M analysis revealed that the low expression of these DERs resulted in a better prognosis (p < 0.05; Figure 3). The other results have been presented in Figure S2.

Table 2

RNAs that were significantly associated with prognosis using multivariate Cox regression analysis

ID Type Coef Hazard ratio z Pr(>|z|)
SOX9-AS1 lncRNA 0.7263754 2.0675728 3.181 0.001466
LINC00665 lncRNA −0.3784111 0.6849489 −1.996 0.04588
LINC01134 lncRNA 0.8595095 2.362002 1.713 0.0486715
FLVCR1 mRNA 1.2147971 3.3696102 3.769 0.000164
DNAJC6 mRNA 1.0555246 2.8734821 3.623 0.000292
SLC7A6 mRNA −1.6519996 0.1916663 −3.529 0.000417
ZWINT mRNA 1.3523435 3.8664762 2.928 0.003416
KIF20A mRNA 1.5733317 4.8226893 2.864 0.004186
CENPF mRNA −1.3804044 0.2514768 −2.507 0.012171
CCNB1 mRNA −0.9717552 0.3784183 −2.175 0.029622
CBX2 mRNA 0.4877579 1.6286604 2.122 0.03384
NQO1 mRNA 0.1078229 1.1138504 2.076 0.037923
SFN mRNA 0.1605477 1.1741538 2.072 0.038287
CCNA2 mRNA 0.4334967 1.5426422 2.021 0.043259
FRAS1 mRNA 0.5390393 1.7143591 1.994 0.046132
SPC24 mRNA −0.5799142 0.5599464 −1.992 0.046388
RECQL4 mRNA −0.6959589 0.4985961 −1.989 0.046662
Figure 3 The K–M curve of the lncRNAs and mRNAs that are significantly correlated with independent prognosis.
Figure 3

The K–M curve of the lncRNAs and mRNAs that are significantly correlated with independent prognosis.

3.4 The expression level of DERs in different clinical groups within the integrated network

Univariate and multivariate Cox regression analyses revealed that the pathologic stage was an independent prognostic clinical factor (Table 3). Consequently, the samples were divided into early (stage 1–2) and advanced (stage 3–4). The K–M curve revealed that patients in the early group had a significantly better prognosis than those in the advanced group (Figure 4a).

Table 3

Univariate and multivariate Cox regression analysis identified independent prognostic clinical factor

Clinical characteristics Univariate Cox Multivariate Cox
HR (95% CI) p value HR (95% CI) p value
Age (years, mean ± SD) 1.012 (0.998–1.026) 4.790 × 10−2 1.011 (0.997–1.026) 1.270 × 10−1
Gender (men/women) 0.817 (0.573–1.164) 2.618 × 10−1 — —
Pathologic M (M0/M1/–) 4.032 (0.763–12.83) 1.057 × 10−1 — —
Pathologic N (N0/N1/–) 2.004 (0.491–8.181) 3.327 × 10−1 — —
Pathologic T (T1/T2/T3/T4/–) 1.675 (0.916–2.007) 1.017 × 10−1 — —
Pathologic stage (I/II/III/IV/–) 1.661 (1.355–2.037) 1.034 × 10−6 1.668 (1.359–2.045) 9.240 × 10−7
Histologic grade (G1/G2/G3/G4) 1.121 (0.887–1.416) 3.392 × 10−1 — —
Vascular invasion (Yes/No/–) 1.351 (0.892–2.047) 1.537 × 10−1 — —
Recurrence (Yes/No/–) 1.375 (0.914–2.068) 1.249 × 10−1 — —
Figure 4 (a) The prognostic K–M curve of patients with different pathologic stages, (b) 12 RNAs expression levels with significant differences in patients of various pathologic stages. (c) Sankey diagram containing lncRNA, m6A enzymes, and mRNAs.
Figure 4

(a) The prognostic K–M curve of patients with different pathologic stages, (b) 12 RNAs expression levels with significant differences in patients of various pathologic stages. (c) Sankey diagram containing lncRNA, m6A enzymes, and mRNAs.

In addition, the expression of 17 DERs between patients in the early and advanced groups was also analyzed. The results indicated that 12 of these DERs exhibited a significantly higher expression level in the advanced group than in the early group (p < 0.05) – including LINC00665, chromobox 2 (CBX2), cyclin A2 (CCNA2), cyclin B1 (CCNB1), centromere protein F (CENPF), FLVCR heme transporter 1 (FLVCR1), Fraser extracellular matrix complex subunit 1 (FRAS1), kinesin family member 20A (KIF20A), recQ like helicase 4 (RECQL4), solute carrier family 7 member 6 (SLC7A6), SPC24 component of NDC80 kinetochore complex (SPC24), and ZW10 interacting kinetochore protein (ZWINT; Figure 4b). The Sankey diagram revealed that LINC00665 was modified by the m6A enzymes IGF2BP1, IGF2BP2, and YTHDF1. Moreover, these three m6A enzymes regulated the methylation of the 11 mRNAs (Figure 4c).

Furthermore, based on the m6A2Target database, we counted the evidence for binding 11 mRNAs, one lncRNA, and three m6A enzymes involved in Figure 4c (Table S2). The results revealed that in the Huh-7 cell line, once IGF2BP1 was knocked down, the expression levels of LINC00665 and ZWINT will be upregulated and downregulated, respectively. In addition, several studies have confirmed a direct interaction between the m6A enzyme and mRNA using eCLIP-seq.

3.5 Verification of the expression of DERs

To analyze the expression of 12 DERs between tumor samples and normal samples, the expression values of these 12 DERs were extracted from the TCGA database. The results indicated that these 12 DERs exhibited a significantly higher expression in the tumor samples than in the normal samples (p < 0.001; Figure 5a). GSE55092 was used to validate the expression of 12 DERs. The results revealed that, except for LINC00665 and FRAS1, all the other 10 mRNAs exhibited significantly higher expression in tumor samples than in normal samples (p < 0.001; Figure 5b).

Figure 5 The relative expression levels of 12 RNAs in (a) TCGA and (b) GSE55092 database between tumor and control samples.
Figure 5

The relative expression levels of 12 RNAs in (a) TCGA and (b) GSE55092 database between tumor and control samples.

4 Discussion

To understand how lncRNAs play a role in HCC by regulating mRNA expression via the modulation of m6A enzymes, 85 and 747 DElncRNAs and DEmRNAs were screened, respectively. A comprehensive network containing m6A proteins, lncRNAs, and mRNAs was constructed. The mRNAs included in this network were primarily involved in the mitotic division, cell cycle checkpoints, and the p53 signaling pathway. It is well established that mitotic cell division is a series of processes designed to accurately propagate the genomic material from a maternal cell into two daughter cells. This process is important for protecting genome integrity [21]. Studies have reported that any disorder in the process of cell division may lead to malignancy [22]. The p53 tumor suppressor gene mutated in more than half of all human malignancies plays a critical role in regulating the cell cycle, cell senescence, and apoptosis and maintaining genomic stability [23]. In addition, there are several reports on the role of p53 in HCC [24].

Following the prognostic and Cox regression analyses, 3 lncRNAs and 14 mRNAs were identified as independent prognostic RNAs. Low expression of these 17 RNAs in TCGA samples was significantly associated with a better prognosis. The samples were further divided into early and advanced stages according to the independent prognostic clinical factor of the pathologic stage, following which 12 RNAs (1 lncRNA and 11 mRNAs) were screened and observed to be expressed significantly differently in various groups. LINC00665 plays a role in cancer development. An earlier study has reported that LINC00665 may be involved in HCC cell cycle regulation, and the high expression of LINC00665 in HCC patients is significantly associated with poor prognosis [25]. This finding is consistent with our observations. Further in vitro experiments confirmed that the depletion of LINC00665 inhibits HCC cell viability and induces cell apoptosis as well as autophagy [26]. However, there have been no studies related to LINC00665 and m6A.

Based on our hypothesis, LINC00665 could regulate 11 mRNAs by modulating the m6A enzymes IGF2BP1, IGF2BP2, and YTHDF1. In lung adenocarcinoma tissues, the expression of LINC00665 is closely related to the aggressive clinicopathological characteristics of patients and can be used as an independent predictor of relapse-free survival [27]. CIP2A-BP is a micropeptide encoded by LINC00665, and its expression in breast cancer cell lines can be downregulated by TGF-b. In breast cancer, downregulated CIP2A-BP expression is associated with tumor metastasis and poor overall survival [28]. It has been earlier reported that LINC00665 can also regulate the occurrence and development of HCC by regulating the expression of cell cycle-related genes CCNA2 and CCNB1 [25]. Further research is necessary to verify whether LINC00665 affects the expression of CCNA2 and CCNB1 via the m6A enzyme. The protein encoded by CCNA2 is a cell cycle regulator [29]. CCNA2 has been proven to be a target of miRNAs that regulate the proliferation of HCC cells [30]. Moreover, as a key promoter of mitosis control, the role of CCNB1 in HCC has also been widely reported. The high expression of CCNB1 is usually closely related to the poor prognosis of HCC patients [31,32]. In this study, the expression of CCNB1 in patients with advanced-stage HCC was significantly higher than that in patients with early stage. It has been reported that CBX2 could regulate proliferation and apoptosis via the phosphorylation of YAP in HCC [33]. High expression of FLVCR1 was significantly associated with poor prognostic value in HCC patients [34]. CENPF was identified as a potential prognostic biomarker and target for HCC [35]. It is reported that upregulated RECQL4 [ 36 ], SPC24 [37], and KIF20A [38] could predict poor prognosis in HCC, whereas upregulated ZWINT was associated with great prognosis in patients with HCC after surgery [39].

m6A2Target database (http://m6a2target.canceromics.org) is the most comprehensive database of target genes corresponding to the three types of m6A enzymes (writers, erasers, and readers) so far. In this database, the validated targets module contains experimentally verified relationship pairs between m6A enzymes and target genes, whereas the Potential Targets module stores the relationship pairs between m6A enzymes and target genes obtained through high-throughput sequencing data analysis. Several studies have confirmed that there was a direct interaction between the m6A enzyme and mRNA using eCLIP-seq [40,41]. However, these results supported by experimental evidence in the database do not include relevant research on HCC. Therefore, further experimental verification is necessary for the correlation between m6A enzyme and target gene in HCC. In conclusion, this study speculated that LINC00665 plays a role in HCC by regulating the above 11 mRNAs via modulation of IGF2BP1, IGF2BP2, and YTHDF1. In so doing, it provided new insights into the roles of lncRNA and m6A enzymes in HCC. Further determination of the regulatory relationship requires more diverse in vivo and in vitro experiments in the future.

Co-first authors.

tel: +86-0871-65902973

  1. Funding information: Authors state no funding involved.

  2. Author contributions: M.L. and X.D. conceived and designed the project. X.L. and F.W. collected the data. M.L. and X.D. performed the interpretation of data. L.G. and F.G. performed the statistical analysis. M.L. and X.D. wrote the manuscript. L.G. and F.G. revised the article. All authors read and approved the final manuscript.

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

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

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Received: 2021-08-19
Revised: 2021-11-05
Accepted: 2021-12-12
Published Online: 2022-02-11

© 2022 Ming Lei et al., published by De Gruyter

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

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
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  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
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  171. Erratum
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  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
https://doi.org/10.1515/biol-2022-0003
Schlagwörter für diesen Artikel
hepatocellular carcinoma; N6-methyladenosine; long noncoding RNA; prognosis; comprehensive network
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
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Heruntergeladen am 22.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0003/html?lang=de
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