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

作者：Lin, Xin; Han, Lu; Gu, Chuncai; Lai, Yihong; Lai, Qiuhua; Li, Qingyuan; He, Chengcheng; Meng, Yan; Pan, Lei; Liu, Side^*; Li, Aimin^*

来源：Aging-US, 2021, 13(5): 7608-7626.

• miR-452-5p
• colorectal cancer
• ERK/MAPK
• PKN2
• DUSP6

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 immunoprecipitation 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.

• 单位
  南方医科大学