کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2130480 | 1086576 | 2012 | 10 صفحه PDF | دانلود رایگان |
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.
Journal: Experimental Cell Research - Volume 318, Issue 17, 15 October 2012, Pages 2168–2177