miR-34a expression in human breast cancer is associated with drug resistance
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Zhi-Hua Li1,*, Xueling Weng2,*, Qiu-Yun Xiong1, Jian-Hong Tu3, An Xiao4, Wei Qiu3, Yu Gong1, Er-Wei Hu1, Songyin Huang2 and Ya-Li Cao1
1Department of Breast Surgery, The Third Hospital of Nanchang City, Key Laboratory of Breast Diseases, Nanchang, Jiangxi 330009, P.R. China
2Guangdong 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
3Department of Pathology, The Third Hospital of Nanchang City, Jiangxi Breast Specialist Hospital, Nanchang, Jiangxi 330009, P.R. China
4Department of Breast Surgery, Pingxiang People’s Hospital, Pingxiang, Jiangxi 330009, P.R. China
*These authors contributed equally to this work
Zhi-Hua Li, email: [email protected]
Ya-Li Cao, email: [email protected]
Songyin Huang, email: [email protected]
Keywords: miR-34a; breast cancer; drug resistance; prognosis
Received: June 03, 2017 Accepted: October 15, 2017 Published: November 06, 2017
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.
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