Microribonucleic Acid-15a-5p Alters Adriamycin Resistance in Breast Cancer Cells by Targeting Cell Division Cycle-Associated Protein 4

Abstract

Jiang-Tao Zhang,1 Jun Chen,2 Hui-Chao Ruan,1 Feng-Xi Li,3 Sen Pang,1 Yu-Ju Xu,1 Dao-Lai Huang,1 Xiang-Hua Wu1 1Department of Gastrointestinal and Gland Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Gastrointestinal Surgery, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Xiang-Hua WuDepartment of Gastrointestinal and Gland Surgery, First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Qingxiu District, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin.Methods: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data.Results: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated.Conclusion: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.Keywords: breast cancer, Adriamycin resistance, miR-15a-5p, CDCA4, cell-free nucleic acids, molecular targets, breast cancer patient stratification

Keywords

• breast cancer
• adriamycin resistance
• mir-15a-5p
• cdca4
• cell-free nucleic acids
• molecular targets
• breast cancer patient stratification