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miR-152-3p Modulates hepatic carcinogenesis by targeting cyclin-dependent kinase 8
Tao Yin1, Ming-Ming Liu2, Ruo-Tian Jin2
1Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100043, China; Department of General Surgery, Affiliated Hospital of Chifeng University, Chifeng 024005, China.
Background:
Cyclin-dependent kinase 8 (CDK8) as a Mediator complex-associated transcriptional regulator has been shown to play important role in the initiation and progression of various cancers. The present study aimed to explore miR-152-3p-modulated post-transcriptional repression of CDK8 in hepatic carcinogenesis.
Methods:
Eighty-nine pairs of hepatocellular carcinoma (HCC) and adjacent non-tumor tissues were collected for molecular biological analysis. Cell viability and apoptosis assays were detected using CCK8 and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexinv-FITC) double staining, respectively. Bioinformatics algorithms and luciferase reporter assay were performed to validate CDK8 as a direct target of miR-152-3p. Gene and protein expression levels were monitored using RT-qPCR, western blotting or immunohistochemical (IHC) staining.
Results:
CDK8 expression levels were up-regulated and miR-152-3p was down-regulated in HCC tissues. The correlation analysis had documented a significant negative correlation between miR-152-3p and CDK8 in the HCC tissues. Both CDK8 and miR-152-3p could serve as the independent prognostic factors for predicting the OS and DFS in HCC patients. Bioinformatics and experimental measurement revealed that CDK8 was a direct target of miR-152-3p. After co-transfection with the miR-152-3p mimics and the CDK8 overexpressed plasmids, the anti-proliferative and pro-apoptotic roles of miR-152-3p were restricted by CDK8.
Conclusion:
The present results obtained forcefully proved that miR-152-3p exhibited an antineoplastic activity via targeting CDK8 and might be served as a potential therapeutic target for the treatment of HCC.
Insights
MicroRNA-152-3p (miR-152-3p) targets Cyclin-dependent kinase 8 (CDK8) to inhibit hepatocellular carcinoma (HCC) growth. This study reveals miR-152-3p as a potential therapeutic agent for HCC, targeting CDK8 to reduce cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Cyclin-dependent kinase 8 (CDK8) is a transcriptional regulator implicated in various cancers.
- Its role in hepatic carcinogenesis warrants further investigation.
- MicroRNAs (miRNAs) are key regulators of gene expression and cancer development.
Purpose of the Study:
- To investigate the role of miR-152-3p in hepatocellular carcinoma (HCC).
- To explore the post-transcriptional regulation of CDK8 by miR-152-3p in HCC.
- To determine the therapeutic potential of miR-152-3p in HCC treatment.
Main Methods:
- Analysis of 89 pairs of HCC and adjacent non-tumor tissues.
- Cell viability (CCK8) and apoptosis (Annexin V/PI staining) assays.
- Bioinformatics, luciferase reporter assays, RT-qPCR, western blotting, and immunohistochemistry to validate target and expression levels.
Main Results:
- CDK8 was upregulated, while miR-152-3p was downregulated in HCC tissues.
- A significant negative correlation was observed between miR-152-3p and CDK8 expression.
- miR-152-3p directly targets CDK8, inhibiting HCC proliferation and promoting apoptosis; both are independent prognostic factors for HCC patients.
Conclusions:
- miR-152-3p exhibits antineoplastic activity in HCC by targeting CDK8.
- miR-152-3p acts as a tumor suppressor in hepatic carcinogenesis.
- miR-152-3p represents a potential therapeutic target for HCC treatment.
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