MicroRNA-493-5p suppresses colorectal cancer progression via the PI3K-Akt-FoxO3a signaling pathway

F.-C. Cui, Y. Chen, X.-Y. Wu, M. Hu, W.-S. Qin

Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, Jinshui District, Zhengzhou City, Henan, P.R. China. facaichn@163.com

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• Oncology

OBJECTIVE: MicroRNA493-5p (miR-493-5p) appears to have an essential role in the abnormal cell proliferation and migration observed in the development and progression of various cancers. However, the function and mechanism of action of miR-493-5p in colorectal cancer (CRC) is unclear.
PATIENTS AND METHODS: MiR-493-5p expression was analyzed in CRC patient tissue samples and cell lines by fluorescence quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). SW480 and Caco-2 cells were transfected with miR-493-5p mimics or treated with the phosphoinositide 3-kinase (PI3K) agonist 740Y-P. Cell proliferation was determined by colony formation and cell proliferation assays and cell migration and invasion by transwell migration and wound-healing assays. The Luciferase reporter assay was used to verify the association between the expression of miR-493-5p and PI3K activity. Expression levels of PI3K, protein kinase B(Akt), and forkhead box O 3a (FoxO3a) proteins were measured by Western blot analysis and immunofluorescence assay.
RESULTS: MiR-493-5p expression was significantly downregulated in CRC tissue samples and cell lines which was associated with progression of CRC. The proliferation, migration, and invasion of CRC cells were inhibited by miR-493-5p overexpression. The finding that miR-493-5p upregulation decreased PI3K, Akt, and FoxO3a protein expression revealed that it directly targets PI3K. Additionally, the miR-493-5p-mediated suppression of CRC cell proliferation, migration and invasion was counteracted by the PI3K agonist, indicating that miR-493-5p suppresses CRC progression by inhibiting the PI3K-Akt-FoxO3a signaling pathway.
CONCLUSIONS: MiR-493-5p suppresses the proliferation, migration, invasion, and progression of CRC via the PI3K-Akt-FoxO3a signaling pathway.

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