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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
MiR-5195-3p targets the PCBP2/PI3K/AKT pathway to inhibit melanoma cell proliferation and migration
Botao Yang1,2, Yucai Wu2, Yang Chen3
1Department of Dermatology, The First Affiliated Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 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.
Insights
MicroRNA-5195-3p suppresses melanoma by targeting poly(rC) binding protein 2 (PCBP2), inhibiting the PI3K/AKT pathway. This discovery offers a potential new therapeutic strategy for melanoma treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA-5195-3p (miR-5195-3p) is recognized as a tumor suppressor in various cancers.
- Its specific role and underlying mechanisms in melanoma remain incompletely understood.
Purpose of the Study:
- To investigate the expression of miR-5195-3p and poly(rC) binding protein 2 (PCBP2) in melanoma.
- To elucidate the functional relationship between miR-5195-3p, PCBP2, and the PI3K/AKT pathway in melanoma.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) and Western blot analysis for gene and protein expression.
- Luciferase reporter assay to confirm direct targeting.
- Cell proliferation (CCK-8) and migration (Transwell) assays.
- Inhibition of the PI3K/AKT pathway using LY294002.
Main Results:
- miR-5195-3p was downregulated, while PCBP2 was upregulated in melanoma tissues.
- PCBP2 was identified as a direct target of miR-5195-3p in melanoma cells.
- Overexpression of miR-5195-3p inhibited melanoma cell proliferation and migration.
- miR-5195-3p suppresses melanoma by inhibiting PCBP2-mediated PI3K/AKT signaling.
Conclusions:
- The miR-5195-3p/PCBP2 axis regulates melanoma cell behavior.
- Targeting the miR-5195-3p/PCBP2/PI3K/AKT pathway presents a promising therapeutic avenue for melanoma.
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