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Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway
Yang Liu1, Juan Tan1, Shuangyan Ou2
1Department of Pathology, Infectious Diseases Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Abstract:
MicroRNAs are involved in each stage of tumor development. Activation of the hepatocyte growth factor (HGF)/c-Met axis facilitates the proliferation and migration of cancer cells, and the HGF/c-MET pathway provides potential targets for anticancer treatment. However, the interaction between HGF and miRNAs in hepatocellular carcinoma (HCC) remains unknown. Previous studies have shown that miR-101 is downregulated in various types of cancer and acts as a tumor suppressor, but the role of miR-101 in HCC has not yet been well defined. Here, we show that HGF is upregulated while microRNA-101-3p is significantly downregulated in the tumor tissues of HCC. By combining bioinformatics analysis and luciferase reporter assays, we demonstrated that HGF is a direct target of miR-101. In vitro experiments indicated that miR-101 inhibits the migration and proliferation of HCC cells by targeting the HGF/c-MET axis, and in vivo studies showed that overexpressed miR-101 dramatically suppresses tumor growth. Therefore, the present study identifies miR-101 as a negative regulator of HGF/c-MET and suggests that miRNAs can be used as targeted drugs for the clinical treatment of HCC.
Insights
MicroRNA-101 (miR-101) suppresses hepatocellular carcinoma (HCC) by targeting the HGF/c-Met pathway. Upregulating miR-101 inhibits tumor growth and cell migration, offering a potential therapeutic strategy for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial in tumor development.
- The hepatocyte growth factor (HGF)/c-Met pathway promotes cancer cell proliferation and migration.
- The role of miR-101 in hepatocellular carcinoma (HCC) requires further definition.
Purpose of the Study:
- To investigate the interaction between HGF and miRNAs in HCC.
- To define the role of miR-101 in HCC progression.
- To explore the therapeutic potential of miR-101 in HCC.
Main Methods:
- Bioinformatics analysis to identify miRNA targets.
- Luciferase reporter assays to confirm direct targeting.
- In vitro cell culture experiments to assess proliferation and migration.
- In vivo studies using animal models to evaluate tumor suppression.
Main Results:
- Hepatocyte growth factor (HGF) was upregulated, while microRNA-101-3p (miR-101) was significantly downregulated in HCC tumor tissues.
- HGF was identified as a direct target of miR-101.
- miR-101 inhibited HCC cell migration and proliferation by targeting the HGF/c-Met axis.
- Overexpression of miR-101 suppressed tumor growth in vivo.
Conclusions:
- miR-101 acts as a tumor suppressor in HCC by negatively regulating the HGF/c-Met pathway.
- miR-101 demonstrates potential as a targeted therapeutic agent for HCC treatment.
- miRNAs represent a promising class of drugs for clinical application in HCC therapy.
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