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.

CircITGA7 regulates malignant phenotypes in bladder cancer cells via targeting miR‐330‐3p/KLF10 axis

“…CircITGA7 is formed from the transcript of the ITGA7 gene, a member of the integrin adhesion molecule family on human chromosome 12 with approximately 256 bp. Low expression of circITGA7 in colorectal cancer tissues has been reported to inhibit colorectal cancer growth by regulating the RAS pathway 13 or by acting as a “sponge” for miR‐3187‐3p 14 and miR‐766 15 . In addition, circITGA7 has been reported to be lowly expressed in gastric cancer 16 and prostate 17 cancer with oncogenic effects.…”

“…Low expression of circITGA7 in colorectal cancer tissues has been reported to inhibit colorectal cancer growth by regulating the RAS pathway 13 or by acting as a "sponge" for miR-3187-3p 14 and miR-766. 15 In addition, circITGA7 has been reported to be lowly expressed in gastric cancer 16 and prostate 17 cancer with oncogenic effects. In some other cancers, such as thyroid cancer, 18 osteosarcoma, 19 and glioma, 20 circITGA7 expression is elevated and exerts a pro-carcinogenic effect.…”