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.
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.
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