Reduced Let-7a Is Associated with Chemoresistance in Primary Breast Cancer

Jiannan Wu; Shunrong Li; Weijuan Jia; Heran Deng; Kai Chen; Liling Zhu; Fengyan Yu; Fengxi Su

doi:10.1371/journal.pone.0133643

Reduced Let-7a Is Associated with Chemoresistance in Primary Breast Cancer

PLoS One. 2015 Jul 28;10(7):e0133643. doi: 10.1371/journal.pone.0133643. eCollection 2015.

Authors

Jiannan Wu¹, Shunrong Li², Weijuan Jia², Heran Deng², Kai Chen², Liling Zhu², Fengyan Yu¹, Fengxi Su¹

Affiliations

¹ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Depart of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, 510120, China.
² Depart of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, 510120, China.

Abstract

Chemotherapy resistance remains an important problem in the breast cancer clinic. The ability to predict the patients who would respond to a distinct therapy would help to optimize tailored treatment options. miRNAs can mediate a number of genes in response to drug-induced acute cellular stress. Several studies suggest that let-7 miRNA may be involved in the chemosensitivity of cancer cell lines in vitro. However, it is not known whether this phenomenon occurs in clinical breast tumors. The present study showed that lower let-7a expression was associated with epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a expression sensitized resistant breast tumor cell lines to epirubicin by enhancing cellular apoptosis in vitro. Collectively, these findings indicate that lower expression of let-7a miRNA can induce chemoresistance in breast cancer by enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic target to modulate epirubicin-based chemotherapy resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Drug Resistance, Neoplasm / drug effects*
Epirubicin / pharmacology*
Female
Gene Expression Regulation, Neoplastic*
Humans
MicroRNAs / biosynthesis*
RNA, Neoplasm / biosynthesis*

Substances

MicroRNAs
RNA, Neoplasm
mirnlet7 microRNA, human
Epirubicin

Grants and funding

This work was supported by the National Natural Science Foundation of China (81472731), the Guangdong Natural Science Funds for Distinguished Young Scholars (S20120011199), the Program for New Century Excellent Talents in University of the Ministry of Education of China and the Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD). This work was also supported by Grant [2013] 163 from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology and Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes.