Circular RNA DENND4C Regulates Cell Malignant Behaviors in Breast Cancer Through the miR-26a-5p/HSPA8 Axis

At present, the potential functions of most circRNAs in breast cancer (BC) have not been fully elucidated. The investigatory research planned to study biological function of circDENND4C in BC and reveal its downstream molecular mechanism.

A total of fifty pairs of BC tissue and their corresponding normal tissue were obtained. circDENND4C/miR-26a-5p/Human 71 kDa heat shock cognate protein (HSPA8) were assessed through RT-qPCR or Western blot. After transfecting the relevant plasmids, MKN-45 cell proliferation, cell cycle, invasion, and migration were assessed through MTT and colony formation assays, flow cytometry, and Transwell tests. Bioinformatics analysis, RIP and dual luciferase reporting experiments verified the interaction between circDENND4C, miR-26a-5p, and HSPA8.

Increased circDENND4C was found in BC and was related to a poor prognosis in BC patients. HSPA8 was upregulated and miR-26a-5p was downregulated in BC. Functionally, silencing circDENND4C prevented cells from proliferation, invasion, and migration, and induced cell cycle arrest at G0/G1 phase. circDENND4C overexpression had the opposite effect. The effects of circDENND4C overexpression or knockdown in BC cells were counteracted by overexpressing miR-26a-5p or HSPA8, respectively. circDENND4C mediated HSPA8 expression by competitively adsorbing miR-26a-5p.

circDENND4C absorbs miR-26a-5p to target HSPA8, thereby promoting BC progression, which provides a new insight into the mechanism of BC.