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PMID: 22101791 Published · ppublish English Journal Article

Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer.

Medical oncology (Northwood, London, England) ·Vol. 29 ·No. 4 ·2012-12-00 ·Pages 2527-34

Chen J, Tian W, Cai H, He H, Deng Y

Abstract

Drug resistance remains a major clinical obstacle to successful treatment in breast cancer patients, and the evidence of microRNAs involvement in cancer drug resistance has been emerging recently. However, the role of microRNA-200c (miR-200c) in modulating chemoresistance of breast cancer remains largely unexplored. Here, we investigated the miR-200c expression in tumor specimens obtained from thirty-nine breast cancer patients who received neoadjuvent chemotherapy by quantitative real-time PCR. Down-regulated miR-200c was observed in non-responders as compared to responders. In addition, miR-200c expression was observed to be down-regulated over 800-fold in human breast cancer cells resistant to doxorubicin MCF-7/ADR as compared to the parental MCF-7 cells. Up-regulation of miR-200c with transfection of miR-200c mimics in breast cancer cells could enhance the chemosensitivity to epirubicin and reduce expression of multidrug resistance 1 mRNA and P-glycoprotein. Moreover, our study demonstrated that restoration of miR-200c in MCF-7/ADR cells could increase intracellular doxorubicin accumulation determined by flow cytometry. Taken together, our findings suggest that miR-200c may act as a promising therapeutic target for improvement of responsiveness to chemotherapy in breast cancer.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters/genetics Adult Breast Neoplasms/drug therapy,genetics Cell Line, Tumor Chemotherapy, Adjuvant Down-Regulation Drug Resistance, Neoplasm Female Humans MicroRNAs/analysis,physiology Middle Aged Neoplasm Proteins/genetics RNA, Messenger/analysis
Chemicals
ABCB1 protein, human ABCG2 protein, human ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters MIRN200 microRNA, human MicroRNAs Neoplasm Proteins RNA, Messenger
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chen Junqing
Department of Surgical Oncology, Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Tian Wei
Cai Hongke
He Haifei
Deng Yongchuan
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Article Info
Journal
Medical oncology (Northwood, London, England)
Abbr.
Med Oncol
ISSN
1559-131X
DOI
10.1007/s12032-011-0117-4
Published
2012-12-00
Epub
2011-00-19
Pages
2527-34
Language
English
Region
United States
NLM ID
9435512
Subset
IM
External Links
PubMed source DOI: 10.1007/s12032-011-0117-4 View journal details
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