Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation

Jin Gao; Yuan Yuan; Lili Zhang; Shaorong Yu; Jianwei Lu; Jifeng Feng; Sainan Hu

doi:10.1186/s12935-020-1164-8

Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation

Cancer Cell Int. 2020 Mar 23:20:90. doi: 10.1186/s12935-020-1164-8. eCollection 2020.

Authors

Jin Gao¹, Yuan Yuan¹, Lili Zhang¹, Shaorong Yu¹, Jianwei Lu¹, Jifeng Feng¹, Sainan Hu²

Affiliations

¹ Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42, Baiziting, Nanjing, 210009, Jiangsu, People's Republic of China.
² Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42, Baiziting, Nanjing, 210009, Jiangsu, People's Republic of China. DrSainanHu@163.com.

Abstract

Background: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Long non-coding RNAs (lncRNAs) are of critical importance in tumor drug resistance. Herein, this study aims to determine the roles of lncRNA ZEB1-AS1 in drug resistance of breast cancer involving microRNA-129-5p (miR-129-5p) and ZEB1.

Methods: Microarray-based gene expression profiling of breast cancer was conducted to identify the differentially expressed lncRNAs. ZEB1 expression was measured in adjacent and cancerous tissues. Next, MCF-7 and MDA-MB-231 cells were treated with a series of inhibitor, mimic or siRNA to clarify the roles of lncRNA ZEB1-AS1 and miR-129-5p in drug resistance of breast cancer. Then the target relationship of miR-129-5p with lncRNA ZEB1-AS1 and ZEB1 was verified. The expression patterns of miR-129-5p, lncRNA ZEB1-AS1, Bcl-2, MDR-1, ZEB1 and corresponding proteins were evaluated. Moreover, the apoptosis and drug resistance of MCF-7 cell were detected by CCK-8 and flow cytometry respectively.

Results: LncRNA ZEB1-AS1 was observed to be an upregulated lncRNA in breast cancer, and ZEB1 overexpression was noted in breast cancerous tissues. MiR-129-5p was revealed to specifically bind to both ZEB1 and lncRNA ZEB1-AS1. Moreover, the expression levels of ZEB1-AS1, ZEB1, Bcl-2, MDR-1, and corresponding proteins were decreased, but the expression of miR-129-5p was increased with transfection of miR-129-5p mimic and lncRNA ZEB1-AS1 siRNA. Besides, drug resistance to cisplatin was inhibited, and cell apoptosis was promoted in breast cancer after transfection of miR-129-5p mimic, lncRNA ZEB1-AS1 siRNA, and ZEB1 siRNA.

Conclusion: In conclusion, the study provides evidence that lncRNA ZEB1-AS1 silencing protects against drug resistance in breast cancer by promoting miR-129-5p-dependent ZEB1 downregulation. It may serve as a novel therapeutic target in breast cancer treatment.

Keywords: Breast cancer; Drug resistance; Long non-coding RNA ZEB1-AS1; ZEB1-AS1/miR-129-5p/ZEB1 signaling pathway.

Publication types

Retracted Publication