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MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop.

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.

SUBMITTER: Lin X

PROVIDER: S-EPMC7993669 | biostudies-literature |

REPOSITORIES: biostudies-literature

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