miR-34a regulates HDAC1 expression to affect the proliferation and apoptosis of hepatocellular carcinoma
Ting-Yi Sun1, Hong-Jian Xie1, Zhen Li1
1Department of Pathology, Henan Provincial People's Hospital Zhengzhou, China.
Abstract:
miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P<0.05), but HDAC1 expression in HCC tissues was markedly higher than in normal tissues (P<0.05). In addition, miR-34a expression was negatively related to HDAC1 expression. miR-34a mimic was transfected into HCC cell lines (HepB3 and HepG2). CCK8 assay, colony formation assay and flow cytometry showed miR-34a over-expression could inhibit the proliferation of HCC cells and induce their apoptosis. Western blotting indicated miR-34a over-expression down-regulated the expression of Bcl-2, procaspase-3, procaspase-9 and c-Myc, but up-regulate p21 expression. Bioinformatics analysis indicated HDAC1 was a target gene of miR-34a. Dual Luciferase Reporter Gene Assay and retrieval assay showed miR-34a could act at the 3'UTR of HDAC1 gene to regulate its expression. Thus, miR-34a may inhibit the proliferation of HCC cells and induce their apoptosis via regulating HDAC1 expression. Our findings provide evidence for the diagnosis and therapeutic target of HCC.
Insights
MicroRNA-34a (miR-34a) inhibits hepatocellular carcinoma (HCC) growth by downregulating histone deacetylase 1 (HDAC1). This study confirms miR-34a
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- MicroRNA-34a (miR-34a) is implicated in tumor suppression.
- The role of miR-34a and its interaction with histone deacetylase 1 (HDAC1) in HCC requires further elucidation.
Purpose of the Study:
- To investigate the functional role of miR-34a in HCC.
- To explore the interaction between miR-34a and HDAC1 in HCC.
- To determine if miR-34a can serve as a diagnostic and therapeutic target for HCC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) to measure miR-34a and HDAC1 expression in 60 HCC tissues.
- Cell transfection with miR-34a mimic in HCC cell lines (HepB3 and HepG2).
- Cell proliferation (CCK8, colony formation) and apoptosis assays (flow cytometry).
- Western blotting to analyze protein expression.
- Bioinformatics analysis, Dual Luciferase Reporter Gene Assay, and retrieval assay to confirm gene targets.
Main Results:
- miR-34a expression was significantly lower in HCC tissues compared to normal tissues.
- HDAC1 expression was significantly higher in HCC tissues compared to normal tissues.
- miR-34a expression was negatively correlated with HDAC1 expression.
- Overexpression of miR-34a inhibited HCC cell proliferation and induced apoptosis.
- miR-34a overexpression altered the expression of apoptosis-related proteins (Bcl-2, procaspase-3, procaspase-9, p21) and c-Myc.
- HDAC1 was identified as a direct target gene of miR-34a, regulated at the 3'UTR.
Conclusions:
- miR-34a plays a crucial role in inhibiting HCC proliferation and inducing apoptosis.
- The mechanism involves the direct regulation of HDAC1 expression by miR-34a.
- miR-34a represents a potential diagnostic biomarker and therapeutic target for hepatocellular carcinoma.
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