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Alterations of microRNAs and their targets are associated with acquired resistance of MCF‐7 breast cancer cells to cisplatin
Author(s) -
Pogribny Igor P.,
Filkowski Jody N.,
Tryndyak Volodymyr P.,
Golubov Andrey,
Shpyleva Svitlana I.,
Kovalchuk Olga
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25191
Subject(s) - microrna , cisplatin , cancer research , mcf 7 , biology , breast cancer , cancer , downregulation and upregulation , cancer cell , phenotype , dna methylation , chemotherapy , gene expression , gene , human breast , genetics
Abstract Cancer cells that develop resistance to chemotherapeutic agents are a major clinical obstacle in the successful treatment of breast cancer. Acquired cancer chemoresistance is a multifactorial phenomenon, involving various mechanisms and processes. Recent studies suggest that chemoresistance may be linked to drug‐induced dysregulation of microRNA function. Furthermore, mounting evidence indicates the existence of similarities between drug‐resistant and metastatic cancer cells in terms of resistance to apoptosis and enhanced invasiveness. We studied the role of miRNA alterations in the acquisition of cisplatin‐resistant phenotype in MCF‐7 human breast adenocarcinoma cells. We identified a total of 103 miRNAs that were overexpressed or underexpressed (46 upregulated and 57 downregulated) in MCF‐7 cells resistant to cisplatin. These differentially expressed miRNAs are involved in the control of cell signaling, cell survival, DNA methylation and invasiveness. The most significantly dysregulated miRNAs were miR‐146a, miR‐10a, miR‐221/222, miR‐345, miR‐200b and miR‐200c. Furthermore, we demonstrated that miR‐345 and miR‐7 target the human multidrug resistance‐associated protein 1. These results suggest that dysregulated miRNA expression may underlie the abnormal functioning of critical cellular processes associated with the cisplatin‐resistant phenotype.