A Novel Circ_0004104/MiR-493-5p/SYPL1 Cascade Contributes to Colorectal Cancer Progression

Abstract

Circular RNAs (circRNAs) play critical roles in human tumorigenesis. Circ_0004104 is abnormally expressed in the tumors of colorectal cancer (CRC). However, its specific function in CRC remains unknown. In this report, we explored the biological action and mechanism of circ_0004104 in CRC development. Quantitative real-time PCR was used to detect circ_0004104, microRNA (miR)-493-5p, and synaptophysin-like 1 (SYPL1) mRNA levels. Fluorescence in situ hybridization (FISH) assay was used to visualize circ_0004104. The impact of circ_0004104 on CRC cell phenotypes was assessed by measuring cell proliferation, migration, invasion, and apoptosis. Animal experiments were performed to analyze the effect of circ_0004104 on CRC xenograft growth in vivo. The potential interacting miRNAs were predicted using the Circular RNA Interactome database, and the binding sites for miR-493-5p in SYPL1 mRNA were predicted using the Starbase3.0 database. The circ_0004104/miR-493-5p and miR-493-5p/SYPL1 relationships were validated by dual-luciferase reporter assay. In CRC tissues and cell lines, circ_0004104 and SYPL1 levels were upregulated and miR-493-5p expression was decreased. Circ_0004104 was mainly located in the cytoplasm of CRC cells and exhibited resistance to RNase R digestion. High circ_0004104 expression predicted a poor prognosis of CRC patients. Functionally, circ_0004104 knockdown suppressed CRC cell proliferation, migration, and invasiveness and accelerated apoptosis in vitro, as well as diminished tumor growth in vivo. Circ_0004104 depletion also decreased N-cadherin and Vimentin levels and increased E-cadherin expression in CRC cells. Mechanistically, circ_0004104 could act as a miR-493-5p sponge, and SYPL1 was a direct target of miR-493-5p. Moreover, circ_0004104 targeted miR-493-5p to regulate SYPL1 expression. The effects of circ_0004104 knockdown on CRC cell behavior alterations were reversed by miR-493-5p inhibitor. Additionally, SYPL1 overexpression reversed the effects of miR-493-5p on CRC cell phenotypes. Our findings suggest that circ_0004104 enhances CRC malignant progression through the miR-493-5p/SYPL1 cascade, providing a potential target for CRC treatment.