MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

Yanqing Su; Yao Lu; Honglin An; Jinhong Liu; Feimin Ye; Jiayu Shen; Zhuona Ni; Bin Huang; Jiumao Lin

doi:10.1021/acsptsci.3c00114

MicroRNA-204-5p Inhibits Hepatocellular Carcinoma by Targeting the Regulator of G Protein Signaling 20

ACS Pharmacol Transl Sci. 2023 Nov 6;6(12):1817-1828. doi: 10.1021/acsptsci.3c00114. eCollection 2023 Dec 8.

Authors

Yanqing Su^{1

2}, Yao Lu^{2

3}, Honglin An², Jinhong Liu^{2

4

5}, Feimin Ye², Jiayu Shen², Zhuona Ni², Bin Huang^{2

4

5}, Jiumao Lin^{2

4

5}

Affiliations

¹ Department of Pharmacy, Xiamen Children's Hospital, Xiamen, Fujian 361006, China.
² Academy of Integrative Medicine of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
³ Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei 050011, China.
⁴ Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
⁵ Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.

PMID: 38093845
PMCID: PMC10714421 (available on 2024-11-06)
DOI: 10.1021/acsptsci.3c00114

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.