Document Detail

miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines.
MedLine Citation:
PMID:  20162574     Owner:  NLM     Status:  MEDLINE    
MicroRNAs (miRNAs) are short noncoding RNA molecules, which posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis and proliferation. Here, we investigated the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. We found that miR-181b was downregulated in both multidrug-resistant human gastric cancer cell line SGC7901/vincristine (VCR) and multidrug-resistant human lung cancer cell line A549/cisplatin (CDDP), and the downregulation of miR-181b in SGC7901/VCR and A549/CDDP cells was concurrent with the upregulation of BCL2 protein, compared with the parental SGC7901 and A549 cell lines, respectively. In vitro drug sensitivity assay demonstrated that overexpression of miR-181b sensitized SGC7901/VCR and A549/CDDP cells to anticancer drugs, respectively. The luciferase activity of a BCL2 3'-untranslated region-based reporter construct in SGC7901/VCR and A549/CDDP cells suggests that a new target site in the 3'UTR of BCL2 of the mature miR-181s (miR-181a, miR-181b, miR-181c and miR-181d) was found. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively. Taken together, our findings suggest that miR-181b could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part, by modulation of apoptosis via targeting BCL2.
Wei Zhu; Xia Shan; Tongshan Wang; Yongqian Shu; Ping Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  127     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2010-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2520-9     Citation Subset:  IM    
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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MeSH Terms
Adenocarcinoma / drug therapy,  genetics*,  metabolism
Apoptosis / drug effects,  genetics
Cell Line, Tumor
Cisplatin / pharmacology
Drug Resistance, Neoplasm
Lung Neoplasms / drug therapy,  genetics*,  metabolism
MicroRNAs / biosynthesis,  genetics*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis,  genetics*
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / drug therapy,  genetics*,  metabolism
Vincristine / pharmacology
Reg. No./Substance:
0/MIRN18A microRNA, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins c-bcl-2; 15663-27-1/Cisplatin; 57-22-7/Vincristine

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