MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells

Bei Zhu; Weixian Chen; Yue Fu; Xiaohan Cui; Lei Jin; Jiadeng Chao; Xiao Yun; Peng Gao; Shiting Shan; Jun Li; Xu Yin; Chunfu Zhu; Xihu Qin

doi:10.2147/OTT.S256153

MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells

Onco Targets Ther. 2020 Jul 14:13:6873-6884. doi: 10.2147/OTT.S256153. eCollection 2020.

Authors

Bei Zhu^{1

2}, Weixian Chen², Yue Fu², Xiaohan Cui¹, Lei Jin², Jiadeng Chao², Xiao Yun^{1

2}, Peng Gao^{2

3}, Shiting Shan^{1

2}, Jun Li^{2

3}, Xu Yin^{1

2}, Chunfu Zhu², Xihu Qin²

Affiliations

¹ Nanjing Medical University, Nanjing 210029, People's Republic of China.
² Department of General Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213000, People's Republic of China.
³ Dalian Medical University, Dalian 116023, People's Republic of China.

Abstract

Aim: This study aimed to explore the regulative mechanisms of miR-27a-3p in chemo-resistance of breast cancer cells.

Materials and methods: qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), colony formation assay, and flow cytometry assay. Moreover, luciferase reporter assay was analyzed to verify the downstream target gene of miR-27a-3p. Further investigation in the correlation between miR-27a-3p and BTG2 was launched by WB, flow cytometry assay, and CCK-8 assay. The expression of Akt and p-Akt was detected by WB.

Key findings: Significantly higher miR-27a-3p expression was confirmed in MCF-7/ADR as compared with sensitive cell line MCF-7 (P<0.05). The down-regulation of miR-27a-3p in MCF-7/ADR enhanced the sensitivity of cancer cells to adriamycin treatment, decreased multidrug resistance gene 1/P-glycoprotein (MDR1/P-gp) expression, enhanced the apoptosis-related proteins expression, increased adriamycin-induced apoptosis, and inhibited cell proliferation as compared to NC groups (P<0.05). The up-regulation of miR-27a-3p in MCF-7 showed the opposite results. BTG2 is identified as a direct target of miR-27a-3p and its down-regulation reversed ADR-resistance. BTG2 treatment exhibited inhibitory effect on PI3K/Akt pathway in MCF-7/ADR cells.

Significance: miR-27a-3p might be associated with resistance of breast cancer cells to adriamycin treatments, modulating cell proliferation and apoptosis by targeting BTG2 and promoting the PI3K/Akt pathway in breast cancer cells. miR-27a-3p/BTG2 axis might be a potential therapeutic target for clinical BC resistance.

Keywords: BTG2; adriamycin; breast cancer; chemoresistance; miR-27a-3p.

Grants and funding

This present work was kindly supported by the Social Development Foundation of Science and Technology of Jiangsu (No. BE2016658), the Changzhou Sci & Tech Program (No.CE20165020), the High-Level Medical Talents Training Project of Changzhou (No.2016CZLJ007), the Project of Changzhou medical innovation team (No.CCX201807), grants from the Natural Science Foundation of China (81702591), and the Natural Science Foundation of Jiangsu Province (BK20170294).