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Published on: June 16, 2022
MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20
Yanqing Su1,2, Yao Lu2,3, Honglin An2
1Department of Pharmacy, Xiamen Children's Hospital, Xiamen, Fujian 361006, China.
Abstract:
Although the oncogenic roles of regulator of G protein signaling 20 (RGS20) and its upstream microRNAs (miRNAs) have been reported, their involvement in hepatocellular carcinoma (HCC) remains unexplored. We utilized the starBase, miRDB, TargetScan, and mirDIP databases, along with a dual-luciferase reporter assay and cDNA chip analysis to identify miRNAs targeting RGS20. miR-204-5p was selected for further experiments to confirm its direct targeting and downregulation of the RGS20 expression. To study the miR-204-5p/RGS20 axis in HCC, RGS20 and miR-204-5p were increased in PLC/PRF/5/Hep3B cells, and the viability, hyperplasia, apoptosis, cell cycle, and invasion/migration of the cells were assessed. RGS20 exhibited optimism, while miR-204-5p exhibited pessimism in tumors. miR-204-5p directly targeted RGS20 and downregulated its expression, whereas high RGS20 expression indicated a poor prognosis. Transfection of miR-204-5p inhibited the hyperplasia, migration, and invasion of HCC cells, but promoted apoptosis and influenced the levels of cyclin-dependent kinase 2 (CDK2), cyclin E1, B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3/8. These effects were reversed by overexpression of RGS20. We recognized miR-204-5p as an upstream regulator targeting RGS20, thereby inhibiting HCC progression by downregulating RGS20 expression. RGS20 may prove to be a potential target for HCC treatment, and miR-204-5p might seem like to be a potential miRNA in gene therapy.
Insights
Regulator of G protein signaling 20 (RGS20) promotes hepatocellular carcinoma (HCC) progression. MicroRNA-204-5p inhibits HCC by targeting and downregulating RGS20, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The role of Regulator of G protein signaling 20 (RGS20) in hepatocellular carcinoma (HCC) is largely unknown.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in cancer development and progression.
Purpose of the Study:
- To investigate the involvement of the miR-204-5p/RGS20 axis in HCC.
- To determine if RGS20 is a direct target of miR-204-5p and to elucidate their functional relationship in HCC cells.
Main Methods:
- Bioinformatic analysis using starBase, miRDB, TargetScan, and mirDIP databases to identify miRNAs targeting RGS20.
- Dual-luciferase reporter assay and cDNA chip analysis to confirm direct targeting.
- Cell viability, proliferation, apoptosis, cell cycle, and invasion/migration assays in HCC cell lines (PLC/PRF/5, Hep3B) with altered miR-204-5p and RGS20 expression.
Main Results:
- miR-204-5p was identified as a direct regulator of RGS20, downregulating its expression in HCC.
- High RGS20 expression correlated with poor prognosis in HCC patients.
- Overexpression of miR-204-5p inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis. These effects were reversed by RGS20 overexpression.
Conclusions:
- miR-204-5p acts as a tumor suppressor in HCC by targeting RGS20 and inhibiting its oncogenic functions.
- RGS20 is a potential therapeutic target for HCC treatment.
- miR-204-5p holds promise as a potential agent for miRNA-based gene therapy in HCC.
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