MicroRNA-27a Promotes the Proliferation and Invasiveness of Colon Cancer Cells by Targeting SFRP1 through the Wnt/β-Catenin Signaling Pathway

Sang Ba, Yi Xuan, Zi-Wen Long, Hai-Yong Chen, Shu-Sen Zheng
Cellular Physiology and Biochemistry 2017, 42 (5): 1920-1933

OBJECTIVE: This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/β-catenin signaling pathway.

METHODS: Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups. RT-qPCR was performed to detect the expressions of miR-27a and SFRP1 mRNA. A dual-luciferase reporter assay was conducted to examine the effect of miR-27a on SFRP1. Western blotting was used to measure the expressions of the SFRP1, β-catenin, GSK-3β, p-β-catenin, p-GSK-3β, c-Myc and cyclin D1 proteins. MTT, soft agar clone formation and Transwell chamber assays were performed to detect cell proliferation and invasion.

RESULTS: Compared with normal tissues and cells, colon cancer tissues and cells demonstrated significantly higher expression of miR-27a, but lower expressions of SFRP1 mRNA and protein. MiR-27a negatively regulated the expression of SFRP1 mRNA. SFRP1 was also found to be a target gene of miR-27a. In the miR-27a mimic group, the proliferation and invasiveness of colon cancer cells were significantly increased, while the expressions of GSK-3 β and p-β-catenin were remarkably down-regulated; in contrast, the expressions of p-GSK-3β, -catenin, c-Myc and cyclin D1 were up-regulated. While the proliferation and invasiveness of colon cancer cells in the anti-miR-27a and Lv-SFRP1 groups were decreased, the expressions of GSK-3β and p-β-catenin were elevated, and the expressions of p-GSK-3β, β-catenin, c-Myc and cyclin D1 were decreased.

CONCLUSION: These findings indicated that miR-27a could promote the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/β-catenin signaling pathway.

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