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  • Title: MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop.
    Author: Lin X, Han L, Gu C, Lai Y, Lai Q, Li Q, He C, Meng Y, Pan L, Liu S, Li A.
    Journal: Aging (Albany NY); 2021 Mar 03; 13(5):7608-7626. PubMed ID: 33658394.
    Abstract:
    BACKGROUND: MiR-452-5p plays an essential role in the development of a variety of tumors, but little is known about its biological function and mechanism in colorectal cancer (CRC). METHODS: The expression levels of miR-452-5p in CRC tissues and cells were detected by real-time quantitative PCR (qRT-PCR). Besides, the biological effects of miR-452-5p on CRC were investigated by functional experiments in vitro and in vivo. Furthermore, bioinformatics analysis, dual-luciferase reporter assay, chromatin immunecipitation assay, western blotting and recovery experiments were implemented to investigate the underlying molecular mechanism. RESULTS: The expression level of miR-452-5p was up-regulated in CRC tissues. MiR-452-5p promoted CRC cell proliferation, cell cycle transition and chemoresistance, and inhibited cell apoptosis. Moreover, miR-452-5p directly targeted PKN2 and DUSP6 and subsequently activated the ERK/MAPK signaling pathway, and it was transcriptionally regulated by c-Jun. CONCLUSION: To conclude, miR-452-5p expression is up-regulated in CRC, which promotes the progression of CRC by activating the miR-452-5p-PKN2/DUSP6-c-Jun positive feedback loop. These findings indicate that miR-452-5p may act as a potential therapeutic target and clinical response biomarker for CRC.
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