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

Abstract

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.

The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells

“…Currently, research on the pathogenicity of colon cancer and the underlying molecular mechanism is still in its infancy [1,2]. The conventional treatment for colon cancer in China consists of surgery, adjuvant therapy, and molecular targeted therapy [3,4].…”

Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations

“…With the help of the MSP, we determined the methylation status of only a few cytosines in the CpG island, thus we cannot exclude the possibility that adjacent cytosines might be methylated, which would result in gene silencing (Hernandez et al 2013). Moreover, recent studies proposed a microRNA-dependent inhibition of SFRP1 in different cancer entities, which may also occur in pediatric liver cancer (Ba et al 2017;. Overall, we identified promoter methylation of SFRP1 in 40% (18/45) of the analyzed cases.…”

<p>Biliverdin Reductase A (BLVRA) Promotes Colorectal Cancer Cell Progression by Activating the Wnt/β-Catenin Signaling Pathway</p>

“…Interestingly, even non-protein regulatory factors, such as miR-27a and miR-590-3p, reportedly promote the proliferation and invasiveness of colon cancer through this pathway. 27,28 Canonical Wnt/β-catenin signaling is also directly linked to its extracellular secretion for tumor progression of colon CSCs. 29 In this pathway, without Wnt, β-catenin cannot accumulate in the cytoplasm as it is phosphorylated by glycogen synthase kinase 3-beta (GSK3β), then ubiquitinated and degraded by the proteasome.…”