Research Paper Volume 13, Issue 5 pp 7608—7626
MiR-452-5p promotes colorectal cancer progression by regulating an ERK/MAPK positive feedback loop
- 1 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
Received: August 21, 2020 Accepted: November 30, 2020 Published: March 3, 2021https://doi.org/10.18632/aging.202657
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Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
CRC: Colorectal cancer; PKN2: protein kinase N2; DUSP6: dual specificity phosphatase 6; PKC: Protein Kinase C; ERK: extracellular regulated protein kinases; MAPK: Mitogen-activated protein kinase; NC: negative control; WT: wild type; 5-FU: 5-Fluorouracil.