Circ_0007351 Exerts an Oncogenic Role In Colorectal Cancer Depending on the Modulation of the miR-5195-3p/GPRC5A Cascade.

Abstract

Circular RNAs (circRNAs) exert critical functions in colorectal cancer development. In this work, we wanted to elucidate the functional role and regulatory mechanism of circ_0007351 in colorectal cancer. For quantification of circ_0007351, microRNA (miR)-5195-3p and G Protein-coupled receptor class C group 5 member A (GPRC5A), a qRT-PCR, immunoblotting or immunohistochemistry assay was performed. Effects of circ_0007351/miR-5195-3p/GPRC5A cascade were evaluated by determining cell viability, proliferation, colony formation, motility, and invasion. Relationships among variables were assessed by dual-luciferase reporter assay. Animal studies were performed to evaluate circ_0007351's function in the growth of xenograft tumors. Circ_0007351 was markedly up-regulated in colorectal cancer tissues and cells. Down-regulation of circ_0007351 hindered cell growth, migration and invasiveness. Also, circ_0007351 depletion exerted a suppressive function in colorectal cell xenograft growth in vivo. Mechanistically, circ_0007351 sponged miR-5195-3p to sequester miR-5195-3p. Reduction of available miR-5195-3p neutralized the effects of circ_0007351 down-regulation on cell phenotypes. MiR-5195-3p directly targeted and inhibited GPRC5A. Circ_0007351 regulated GPRC5A expression by sponging miR-5195-3p. Moreover, the effects of circ_0007351 down-regulation on cell functional phenotypes were due to in part the reduction of GPRC5A expression. Our findings show that circ_0007351 down-regulation impedes proliferation, motility, and invasiveness in colorectal cancer cells at least in part via the regulation of the miR-5195-3p/GPRC5A cascade, highlighting that circ_0007351 inhibition may have a potential therapeutic value for colorectal cancer.