文献类型：期刊文献

英文题名：MiR-222 modulates multidrug resistance in human colorectal carcinoma by down-regulating ADAM-17

作者：Xu, Ke[2,3];Liang, Xin[2,3];Shen, Ke[2,3];Sun, Liyun[2,3];Cui, Daling[2,3];Zhao, Yuxia[2,3];Tian, Jianhui[1];Ni, Lei[4];Liu, Jianwen[2,3]

机构：[1]Shanghai Univ Tradit Chinese Med, Natl Clin Res Ctr Tradit Chinese Med & Oncol, Longhua Hosp, Dept Oncol, Shanghai 200032, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Respirat, Shanghai 200025, Peoples R China

年份：2012

卷号：318

期号：17

起止页码：2168

外文期刊名：EXPERIMENTAL CELL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000308385600002)】；

基金：This work was supported by the Shanghai Committee of Science and Technology (Grant no. 11DZ2260600), and National Natural Science Foundation of China (NSFC Project Number: 81173224).

语种：英文

外文关键词：Colorectal carcinoma; Multidrug-resistance (MDR); MiR-222; ADAM-17; TGF-alpha; EGFR

摘要：Colorectal carcinoma is a frequent cause of cancer-related death in men and women throughout the world. MicroRNAs are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. We investigated the role of ADAM-17 (a desintegrin and metalloproteases 17) as a novel multidrug resistance (MDR) mechanism in multidrug-resistant colorectal carcinoma (CRC) and the role of miR-222 in the development of MDR in CRC cells. We found that the high expression of ADAM-17, which results in growth factor shedding and growth factor receptor activation could induce drug resistance in CRC. Pharmacological inhibition of ADAM-17, in conjunction with chemotherapy, may have therapeutic potential for the treatment of CRC. ADAM-17 is a predicted target of miR-222, which was downregulated in multidrug-resistant CRC cells. The presence of miR-222 was consistently inversely proportionate to the expression levels of ADAM-17. We found that elevated levels of miR-222 in the mimics-transfected HCT116/L-OHP and HCT-8/VCR cells reduced the ADAM-17 protein level and the luciferase activity of an ADAM-17 3' untranslated region-based reporter and sensitized these cells' apoptosis to some anticancer drugs. Our findings suggest that miR-222 could play a role in the development of MDR by modulation of ADAM-17, the new MDR treatment target in colorectal carcinoma cells. (c) 2012 Elsevier Inc. All rights reserved.