OncoTargets and Therapy (May 2020)
MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest
Abstract
Yang Wang, Nan Wu, Jun Zhang, Huidong Wang, Xiaojuan Men Department of Galactophore Surgery, Weifang People’s Hospital, Weifang, Shandong 261041, People’s Republic of ChinaCorrespondence: Xiaojuan MenDepartment of Galactophore Surgery, Weifang People’s Hospital, Weifang, Shandong 261041, People’s Republic of ChinaEmail [email protected]: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triple-negative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells.Methods: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally.Results: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model.Conclusion: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR‑153-5p may be a promising agent for patients with PTX-resistant TNBC.Keywords: triple-negative breast cancer, paclitaxel, miR-153-5p, CDK1, cell cycle