Circ_0009035 regulates the progression of cervical cancer by targeting miR-1305/CREBRF axis.

Abstract

Circular RNAs (circRNAs) have a crucial role in the occurrence of many diseases, such as tumors. Yet the roles of circ_0009035 (circRACGAP1) in cervical cancer are not fully characterized. The expression levels of circRACGAP1, miR-1305 and cAMP-responsive element-binding protein 3 regulatory factor (CREBRF) were detected by using real-time quantitative PCR or western blot. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine, colony formation assay, transwell assay and tube formation assay were used to detect cell proliferation, migration and invasion and angiogenesis, respectively. Flow cytometry assay was used to analyze the cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to analyze the targeting about miR-1305 and circ_0009035 or CREBRF. Xenograft model was built to study the role of circ_0009035 in vivo. Immunohistochemistry was used to detect the expression of Ki67, epithelial cadherin and vimentin. First, we found that circ_0009035 expression was significantly upregulated in tumor cells and tissues; second, knockdown of circ_0009035 could inhibit cell proliferation, migration and invasion and promote cell apoptosis. Subsequently, circ_0009035 was found to be able to target miR-1305, and the expression of miR-1305 in tumor tissues and cells was significantly lower. MiR-1305 inhibitor could restore cell-related progression of cervical cancer inhibited by si-circ_0009035. Finally, miR-1305 could target CREBRF, and circ_0009035 could regulate CREBRF expression by targeting miR-1305, thereby affecting cervical cancer tumorigenesis. In summary, our study confirmed that circ_0009035 could influence the development of cervical cancer through the targeted regulation of miR-1305/CREBRF.