MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL
Gehao Liang, Yun Ling, Qun Lin, Yu Shi, Qing Luo, Yinghuan Cen, Maryam Mehrpour, Ahmed Hamaï, Jun Li, Chang Gong
Abstract
Objectives Circular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2 – ) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2 + ) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear. Materials and methods qRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed. Results CircCDYL was high-expressed in HER2 + breast cancer tissue, similar with that in HER2 – breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2 + breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2 + breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2 + breast cancer patients. Conclusion MiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2 + breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2 + breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2 + breast cancer patients.