MiR-139-5p influences hepatocellular carcinoma cell invasion and proliferation capacities via decreasing SLITRK4 expression

Jisiguleng, Wu; Zhang, Tong; Chen, Yubo; Ha, Sigaowa

doi:10.1042/bsr20193295

Cited by 22 publications

(24 citation statements)

References 36 publications

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“…Consistent with previous reports [32][33][34], our results revealed that the downregulation of miR-139-5p showed a significant association with worse survival in HCC patients. According to CCT5 mRNA expression and its associations with OS and clinico-pathological features in HCC patients.…”

Section: Discussionsupporting

confidence: 93%

“…existing publications, miR-139-5p inhibits HCC progression by targeting several genes, such as ZEB1 and ZEB2 [31], EZH2 [52], SPOCK1 [32], ETS1 [33], XIST [53] and SLITRK4 [34]. MiR-139-5p was confirmed to negatively regulate ZEB1 and ZEB2 expression [31], which induces EMT and promotes the progression of malignant carcinoma [54], while overexpression of ZEB1 and ZEB2 abolishes the inhibitory effects of miR-139-5p on HCC cell migration and invasion [31].…”

Section: Discussionmentioning

confidence: 99%

“…In HCC, miR-139-5p functions to inhibit EMT and metastasis by targeting zinc finger E-box binding to homeobox 1 (ZEB1) and ZEB2, and its expression is downregulated in HCC cells and tumor tissues [31,32]. MiR-139-5p inhibited HCC cell viability, migration and invasion and induced apoptosis by targeting kazal-like domains proteoglycan 1 (SPOCK1), E26 transformation-specific 1 (ETS1) and NTRK like family member 4 (SLITRK4) [32][33][34]. Given the controversial role of miR-139-5p in human malignancies and the importance of identifying target genes of miR-139-5p in HCC, we conducted an integrated bioinformatic analysis to investigate the roles and target genes of miR-139-5p in HCC patients.…”

Section: Ivyspringmentioning

confidence: 99%

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Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Xu¹,

Zhang²,

Liu³

et al. 2021

Int. J. Med. Sci.

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Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC. Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established. Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively. Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

See 1 more Smart Citation

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Xu¹,

Zhang²,

Liu³

et al. 2021

Int. J. Med. Sci.

View full text Add to dashboard Cite

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“…Consistent with our results, other studies showed down-regulation of miR-139-5p in HCC samples. 25,26 Its low Magnification, ×100 (G), ×200 (H). HCC, hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma

Yang¹,

Qiu²,

Lin³

et al. 2021

Journal of Clinical and Translational Hepatology

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Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PP-P2CA may be involved in HCC were determined using miR-Walk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PP-P2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

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“…Many studies showed that miRNAs participated in the biological behavior of HCC. For instance, miR-139-5p in uenced HCC cell invasion and proliferation capacities by decreasing the expression of SLITRK4 [9].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

Tian

Hong

et al. 2020

Preprint

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Abstract Background:Mitogen-inducible gene 6 (Mig-6) is a tumor suppressor gene that plays an important role in many types of cancers by interacting with EGFR. Thus far, little is known about the molecular mechanism of Mig-6 in hepatocellular carcinoma (HCC). Also, the relationship between Mig-6 and miRNAs needs to be elucidated. Therefore, this study first aimed to find whether Mig-6 could promote apoptosis and inhibition of the flux of autophagy by its downstream miRNA in HCC cell lines. Methods: Two cell lines, HepG2and HLE, were used in this study. Mig-6 overexpression and knockdown models , miR-193a mimics and inhibitors models,were established. MiRNA microarray profiling were used to verified Mig-6 regulated- miRNA. Real-time PCR, Western blot analysis were carried out to detect RNA and protein expression.Evaluation of fluorescent LC3 puncta and cell fow cytometer assay were used to test the autophagy and apoptosis respectively. Results: Mig-6 induced the apoptosis and reduced the autophagy of HCC cell lines. MiR-193a-3p is a Mig-6-regulated miRNA in Mig-6 overexpression model, and miR-193a-3p affected the apoptosis and autophagy of HCC cells by regulating the expression of TGF-β2. Additionally, the relationship between Mig-6 and transforming growth factor TGF-β2 was explored in depth for the first time.Conclusion:These findings revealed an important regulatory axis Mig-6/miR-193a-3p/TGF-β2 in the apoptosis and autophagy of HCC cells, providing a novel insight into the therapeutic target in HCC.

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MiR-139-5p influences hepatocellular carcinoma cell invasion and proliferation capacities via decreasing SLITRK4 expression

Cited by 22 publications

References 36 publications

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

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