MiR-5195-3p targets the PCBP2/PI3K/AKT pathway to inhibit melanoma cell proliferation and migration

Botao Yang; Yucai Wu; Yang Chen; Yongshuang Li; Jinhua Wang; Xushan Cha; Jing Liu

doi:10.1016/j.heliyon.2023.e19227

MiR-5195-3p targets the PCBP2/PI3K/AKT pathway to inhibit melanoma cell proliferation and migration

Heliyon. 2023 Aug 19;9(9):e19227. doi: 10.1016/j.heliyon.2023.e19227. eCollection 2023 Sep.

Authors

Botao Yang^{1

2}, Yucai Wu², Yang Chen³, Yongshuang Li⁴, Jinhua Wang⁵, Xushan Cha¹, Jing Liu¹

Affiliations

¹ Department of Dermatology, The First Affiliated Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
² Department of Dermatology, Guangdong Provincial People's Hospital's Nanhai Hospital, Foshan, Guangdong Province, China.
³ Department of Dermatology, Yangjiang People's Hospital, Yangjiang, Guangdong Province, China.
⁴ Department of Dermatology, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong Province, China.
⁵ Department of Dermatology, The Affiliated Shunde Hospital of Jinan University, Foshan City, Guangdong Province, China.

Abstract

Although miR-5195-3p has been acknowledged for its tumor suppressor role in diverse cancer categories, its precise functions and mechanisms concerning melanoma have not been comprehensively elucidated. In this study, we employed quantitative reverse transcription PCR, Western blot analysis, and immunohistochemistry staining to investigate the expression patterns of miR-5195-3p and poly (rC) binding protein 2 (PCBP2) in melanoma tissues compared to adjacent tissues. Our findings revealed downregulation of miR-5195-3p and upregulation of PCBP2 in melanoma tissues. Through the implementation of a luciferase reporter assay, we successfully identified PCBP2 as a newly discovered target of miR-5195-3p in melanoma cells. Enforced expression of miR-5195-3p via mimics inhibited cell proliferation and migration in A375 and A2058 cells, as demonstrated by CCK-8 and transwell migration assays. In melanoma cells, reintroduction of PCBP2 partially reversed the inhibitory effects of miR-5195-3p overexpression. Treatment with LY294002, an inhibitor of the PI3K/AKT signaling pathway, also reversed the effects of PCBP2 in melanoma cells. Furthermore, our results suggest that miR-5195-3p inhibits the activation of the PI3K/AKT signaling pathway in melanoma by inhibiting PCBP2. In conclusion, our research has identified the miR-5195-3p targeting of the PCBP2-mediated PI3K/AKT signaling pathway as a potential therapeutic target for melanoma treatment.

Keywords: MIRN5195-3p; Melanoma; PI3K/AKT signaling; Poly(rC) binding protein 2.