Knockdown of circ-ADAM9 inhibits malignant phenotype and enhances radiosensitivity in breast cancer cells via acting as asponge for miR-383-5p.

Abstract

Circular RNA (circRNA) has been proven to play acritical role in breast cancer progression. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circ-disintegrin and metalloproteinase9 (circ-ADAM9) in breast cancer. Aquantitative real-time polymerase chain reaction (RT-qPCR) was conducted to assess the expression levels of circ-ADAM9, microRNA-383-5p (miR-383-5p), and profilin2 (PFN2). Cellular growth curves of breast cancer cells were determined by colony-forming assay. Cell viability and apoptosis were measured by MTT and flow cytometry, respectively. The protein expression level was analyzed by western blot. Cell migration and invasion were evaluated by wound healing and Transwell assays. Axenograft experiment was established to clarify the functional role of circ-ADAM9 inhibition in vivo. The interactions among circ-ADAM9, miR-383-5p, and PFN2 were analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. We found that circ-ADAM9 was upregulated in breast cancer tissues and cells compared to controls. Inhibition of circ-ADAM9 expression impaired proliferation, migration, and invasion, but increased radiosensitivity and apoptosis in breast cancer cells; besides, radiotherapy combined with circ-ADAM9 inhibition showed significant inhibitory effects on tumor growth. The functional effects of circ-ADAM9 were related to miR-383-5p, atarget of circ-ADAM9. Overexpression of miR-383-5p-mediated malignant behaviors and radiosensitivity of breast cancer cells were dependent on PFN2. Circ-ADAM9 was found to participate in breast cancer progression through targeting the miR-383-5p/PFN2 axis.