Circ-PRMT5 promotes breast cancer by the miR-509-3p/TCF7L2 axis activating the PI3K/AKT pathway

Background Breast cancer is the most prevalent malignancy occurring in females. In recent years, emerging evidence has suggested that circular RNAs are involved in the development of multiple cancers. Circ-PRMT5 has recently attracted attention as a tumor-promoting circular RNA. In the present study, we focused on exploring the biological effects of circ-PRMT5 in breast cancer. Methods A quantitative real-time polymerase chain reaction was used to determine the expression of circ-PRMT5 in breast cancer. In vitro experiments, including cell-counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry and tube formation assays, were performed to test the effects of circ-PRMT5 on the cellular progression of breast cancer. Bioinformatic analysis, luciferase reporter, radioimmunoprecipitation and RNA-pull down assays were performed to predict the potential microRNAs interacting with circ-PRMT5 and mRNAs that can be targeted by miR-509-3p. Results Circ-PRMT5 is up-regulated in breast cancer tissues and cells. Importantly, an elevation of circ-PRMT5 indicates a poor prognosis in patients with breast cancer. Functionally, knockdown of circ-PRMT5 suppresses cell proliferation and angiogenesis and increases cell apoptosis in breast cancer. Mechanistically, we identified that circ-PRMT5 up-regulates TCF7L2 expression by acting as a miR-509-3p sponge. The negative expression correlation between miR-509-3p and circ-PRMT5 or TCF7L2 in clinical tissues was further demonstrated. Rescue assays showed that TCF7L2 overexpression reverses the antitumoral effects of circ-PRMT5 knockdown on breast cancer cell processes. Additionally, we demonstrated that circ-PRMT5 activates the phosphoinositide 3-kinase (PI3K)/AKT pathway by up-regulation of TCF7L2. Conclusions Overall, our data indicate that the circ-PRMT5/miR-509-3p/TCF7L2 axis can aggravate the malignant character of breast cancer cells by the regulation of the PI3K/AKT pathway.