CircRNA SMARCC1 Sponges MiR-140-3p to Regulate Cell Progression in Colorectal Cancer

Cancer Manag Res. 2020 Jun 23:12:4899-4910. doi: 10.2147/CMAR.S254185. eCollection 2020.

Abstract

Purpose: Our objective was to investigate the effect of circSMARCC1 on the developmental and biological behavior of colorectal cancer (CRC).

Materials and methods: The expression of circSAMRCC1 and miR-140-3p in CRC tissues and cell lines (SW620, HCT116, HT29 and SW480) and a normal cell line (NCM460) was detected using qRT-PCR. The expression levels of circSMARCC1 and its linear subtype were detected. Fluorescence in situ hybridization was performed for the evaluation of the localization of circSAMRCC1 and miR-140-3p in the SW620 cell line. The effects of circSAMRCC1 and miR-140-3p on cell proliferation were investigated using CCK8 and colony formation assays, respectively. The effects of circSAMRCC1 and miR-140-3p on cell migration and invasion were determined using Transwell assay. The binding relationship between circSMARCC1 and miR-140-3p was further assessed by bioinformatics, ChIRP analysis and double luciferase reporter assay.

Results: The expression of circSAMRCC1 in the CRC tissues and four cell lines is significantly increased, and circSMARCC1 and miR-140-3p are negatively correlated with expression level in the tissue. The downregulation of circSMARCC1 decreased CRC cell viability and suppressed metastasis in vitro and Inhibition of protein (MMP-2, MMP-9, VEGF) expression. miR-140-3p is downregulated in CRC tissues; miR-140-3p mimics inhibited SW620 cell viability, migration and invasion, and miR-140-3p inhibitors reversed the the effect of circSMARCC1 downregulation on cell proliferation, migration and invasion in CRC cells.

Conclusion: circSMARCC1 competitively combined with miR-140-3p and functioned through a circSMARCC1/miR-140-3p/MMPs axis as a CRC carcinogen, demonstrating its potential as a biomarker for CRC treatment.

Keywords: MMP pathway; cell proliferation; circSAMRCC1; colorectal cancer; miR-140-3p.