Open AccessMiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop
Author(s) -
Lin Xin,
Lu Han,
Chun-Cai Gu,
Yihong Lai,
Qiuhua Lai,
Qingyuan Li,
Chengcheng He,
Yan Meng,
Lei Pan,
Side Liu,
Aimin Li
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202657
Subject(s) - mapk/erk pathway , colorectal cancer , medicine , oncology , cancer research , cancer , biology , kinase , microbiology and biotechnology
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.