miR-34a expression in human breast cancer is associated with drug resistance

// Zhi-Hua Li 1, * , Xueling Weng 2, * , Qiu-Yun Xiong 1 , Jian-Hong Tu 3 , An Xiao 4 , Wei Qiu 3 , Yu Gong 1 , Er-Wei Hu 1 , Songyin Huang 2 and Ya-Li Cao 1 1 Department of Breast Surgery, The Third Hospital of Nanchang City, Key Laboratory of Breast Diseases, Nanchang, Jiangxi 330009, P.R. China 2 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China 3 Department of Pathology, The Third Hospital of Nanchang City, Jiangxi Breast Specialist Hospital, Nanchang, Jiangxi 330009, P.R. China 4 Department of Breast Surgery, Pingxiang People’s Hospital, Pingxiang, Jiangxi 330009, P.R. China * These authors contributed equally to this work Correspondence to: Zhi-Hua Li, email: huazhili0802@163.com Ya-Li Cao, email: caoyali@medmail.com.cn Songyin Huang, email: hsongyin@126.com Keywords: miR-34a; breast cancer; drug resistance; prognosis Received: June 03, 2017      Accepted: October 15, 2017      Published: November 06, 2017 ABSTRACT miR-34a is significantly down-regulated in breast cancer tissues and cell lines, which may be correlated with breast cancer multi-drug resistance (MDR). Here, we conducted cell-based experiments and clinical studies in a cohort of 113 breast cancer samples to analyze miR-34a expression and breast cancer MDR. Expression of miR-34a is down-regulated in the multi-drug resistant MDR-MCF-7 cells compared with its parental cells. Patients with miR-34a low expression had poorer overall survival (OS) and disease free survival (DFS) in comparison with those with high expression. Transfecting miR-34a mimics into MDR-MCF-7 breast cancer cells led to partial MDR reversal. Compared with the control group, miR-34a significantly reduced both the mRNA and protein expressions of BCL-2, CCND1 and NOTCH1, but no obvious changes were found in P53 or TOP-2a expression. In breast cancer tissue samples, the expression of miR-34a was related to BCL-2, CCND1 and NOTCH1, but not to HER-2, P53 and TOP-2a. Altogether, our findings suggest that miR-34a is an MDR and prognosis indicator of breast cancer, which may participate in the regulation of drug-resistant breast cancer by targeting BCL-2, CCND1, and NOTCH1.