circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma.

ABSTRACT

Circular RNAs have been reported to be widely involved in cancer cell tumorigenesis and drug resistance; here, the aim of this study was to investigate whether circRNA Integrin Subunit Alpha 7 (ITGA7) (circ_ITGA7) was associated with the tumor growth and radiosensitivity of colorectal cancer (CRC). We found that circ_ITGA7 expression was lower in CRC tissues and cells than those in the normal tissues and cell lines according to quantitative real-time polymerase chain reaction. As shown by cell counting kit-8 assay, flow cytometry, colony formation assay, and xenograft experiment, ectopic overexpression of circ_ITGA7 remarkably restrained CRC tumor growth and enhanced radiosensitivity in vitro and in vivo. Mechanistically, circ_ITGA7 could target microRNA (miR)-766 to prevent the degradation of its target gene mothers against decapentaplegic homolog 4 (SMAD4), the binding between miR-766 and circ_ITGA7 or SMAD4 was first verified by dual-luciferase activity assay. Additionally, miR-766 up-regulation reversed the inhibitory effects of circ_ITGA7 on CRC growth and radiosensitivity. Besides that, inhibition of miR-766 reduced CRC cell growth and sensitized cells to radiotherapy, and these effects mediated by miR-766 inhibitor were rescued by the silencing of SMAD4. In all, circ_ITGA7 suppressed CRC growth and enhanced radiosensitivity by up-regulating SMAD4 through sequestering miR-766, providing an insight for the further development of CRC treatment.