MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop.
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.
['Lin|Xin|X|', 'Han|Lu|L|', 'Gu|Chuncai|C|', 'Lai|Yihong|Y|', 'Lai|Qiuhua|Q|', 'Li|Qingyuan|Q|', 'He|Chengcheng|C|', 'Meng|Yan|Y|', 'Pan|Lei|L|', 'Liu|Side|S|', 'Li|Aimin|A|']
D017209:Apoptosis D015153:Blotting, Western D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D047369:Chromatin Immunoprecipitation D015179:Colorectal Neoplasms D018450:Disease Progression D054642:Dual Specificity Phosphatase 6 D015972:Gene Expression Regulation, Neoplastic D006801:Humans D020935:MAP Kinase Signaling System D035683:MicroRNAs D011493:Protein Kinase C D060888:Real-Time Polymerase Chain Reaction D015854:Up-Regulation
miR-452-5p colorectal cancer ERK/MAPK PKN2 DUSP6