circ-ZEB1 regulates epithelial-mesenchymal transition and chemotherapy resistance of colorectal cancer through acting on miR-200c-5p

Circular RNAs (circRNAs) have been demonstrated to be important regulators in human malignant tumors, including colorectal cancer (CRC). While the role circ-ZEB1 played in CRC remains unclear. In this study, we aim to explore the biological function and the underlying mechanism of circ-ZEB1 in CRC. RNAscope was used to analyze the expression and localization of circ-ZEB1 in CRC tissues. Loss of function experiments were con-ducted, including CCK-8, transwell assays, flow cytometry analysis, and murine xenograft models, so as to detect the effect of circ-ZEB1 on CRC cells. IC50 assay was used to evaluate the influence of circ-ZEB1 on the che-moresistance of CRC cells. Epithelial-mesenchymal transition (EMT) related markers were detected. The rela-tionship between circ-ZEB1 and miR-200c-5p was investigated by FISH, dual-luciferase reporter assay, and RIP assay. We found in our study that circ-ZEB1 was significantly upregulated in CRC tissues. Downregulation of circ-ZEB1 inhibited cell proliferation, colony formation, as well as cell migration and invasion abilities of CRC cell lines. In vivo experiments indicated that knockdown of circ-ZEB1 suppressed tumorigenesis and distant metas-tasis of CRC cells in nude mice. What's more, EMT and chemoresistance of CRC cells were also attenuated following circ-ZEB1 knockdown. Mechanistically, we proved that circ-ZEB1 could directly bind with miR-200c and functioned as miR-200c sponge to exert its biological functions in CRC cells. In conclusion, circ-ZEB1 could promote CRC cells progression, EMT, and chemoresistance via acting on miR-200c, elucidating a poten-tial therapeutic target to inhibit CRC progression.

Automated summary

This study found that circ-ZEB1 is significantly upregulated in colorectal cancer tissues. Downregulation of circ-ZEB1 can inhibit the proliferation, migration, and invasion abilities of colorectal cancer cells, as well as attenuate the epithelial-mesenchymal transition and chemoresistance. Mechanistically, circ-ZEB1 can directly bind with miR-200c and function as a sponge to regulate its biological functions in colorectal cancer cells. These findings elucidate circ-ZEB1 as a potential therapeutic target to inhibit the progression of colorectal cancer.