OncoTargets and Therapy (May 2020)

MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest

  • Wang Y,
  • Wu N,
  • Zhang J,
  • Wang H,
  • Men X

Journal volume & issue
Vol. Volume 13
pp. 4089 – 4097

Abstract

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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

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