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In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
Mir-765 promotes cell proliferation by downregulating INPP4B expression in human hepatocellular carcinoma
Bin-Hui Xie1, Xiao He1, Rui-Xi Hua2
1Department of General Surgery, the First Affiliated Hospital of Gannan Medical University, Guangzhou, Guangdong, China.
Abstract:
microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively. Overexpression of mir-765 increased HCC cells proliferation and tumorigenicity, whereas inhibition of mir-765 reverses this effect. Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 repressed INPP4B expression, resulting in upregulation of p-AKT, Cyclin D1, and downregulation of p-FOXO3a, p21 expression in HCC. Strikingly, we found that silencing the expression of INPP4B is the essential biological function of miR-765 during HCC cell proliferation. Collectively, our findings reveal that miR-765 is a potential onco-miR that participates in carcinogenesis of human HCC by suppressing INPP4B expression, and might represent a potential therapeutic target for HCC patients.
Insights
MicroRNA-765 (miR-765) promotes hepatocellular carcinoma (HCC) growth by targeting INPP4B. Inhibiting miR-765 may offer a new therapeutic strategy for HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysregulation is implicated in cancer progression, including sustained cell proliferation.
- Understanding miRNA mechanisms in carcinogenesis is crucial for improving cancer diagnostics and therapeutics.
Purpose of the Study:
- To investigate the role of miR-765 in hepatocellular carcinoma (HCC) development.
- To identify the molecular targets and pathways regulated by miR-765 in HCC.
Main Methods:
- Quantitative real-time PCR to assess miR-765 expression in HCC cell lines and tissues.
- Cell proliferation and tumorigenicity assays following miR-765 overexpression or inhibition.
- Western blotting to analyze protein expression levels of INPP4B, AKT, Cyclin D1, FOXO3a, and p21.
Main Results:
- miR-765 was significantly upregulated in HCC cell lines and tissues compared to normal controls.
- Overexpression of miR-765 enhanced HCC cell proliferation and tumorigenicity, while inhibition reversed these effects.
- miR-765 directly targets INPP4B, leading to decreased INPP4B expression and subsequent modulation of AKT, Cyclin D1, FOXO3a, and p21 signaling pathways.
Conclusions:
- miR-765 acts as an onco-microRNA in human HCC by suppressing INPP4B expression.
- miR-765 plays a critical role in HCC cell proliferation through the miR-765/INPP4B axis.
- miR-765 represents a potential diagnostic biomarker and therapeutic target for HCC.
Related Concept Videos
Abnormal Proliferation
Inhibition of Cdk Activity
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