کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2815518 1159874 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Downregulation of miR-363 increases drug resistance in cisplatin-treated HepG2 by dysregulating Mcl-1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
Downregulation of miR-363 increases drug resistance in cisplatin-treated HepG2 by dysregulating Mcl-1
چکیده انگلیسی


• Cisplatin treatment results in downregulation of miR-363 and upregulation of Mcl-1.
• MiR-363 decreases cell viability during cisplatin treatment in HepG2-R cells.
• MiR-363 directly targets Mcl-1 and inhibits its expression in HepG2-R cells.
• MiR-363 decreasing cisplatin resistance by inhibiting Mcl-1 expression

Systemic therapy with cytotoxic agents provides marginal benefit in hepatocellular carcinoma (HCC) treatment especially for patients with advanced HCC. Cisplatin is one of the most active cytotoxic agents for HCC treatment. However, acquisition of cisplatin resistance is common, and one important underlying mechanism of such resistance is apoptosis-resistance. In this study, we found that miR-363 levels were significantly decreased in HCC patients treated with cisplatin-based chemotherapy. MiR-363 levels were also lower in cisplatin-resistant HepG2 (HepG2-R) cells than in HepG2 cells. Exogenous miR-363 significantly overcame cisplatin resistance in HepG2-R cells, whereas miR-363 knockdown increased the cell viability during cisplatin treatment. We further demonstrated that miR-363 directly targeted to Mcl-1 3′-UTR (3′-Untranslated Regions). Downregulation of miR-363 resulted in upregulation of Mcl-1 which is a key member of anti-apoptotic Bcl-2 family and increased drug resistance. We finally demonstrated that miR-363 decreased cisplatin resistance of HCC cell, partly by targeting Mcl-1. These data suggest that the combination of miR-363 and cisplatin may represent a novel approach in treatment for HCC, thus offering a new target for chemotherapy of HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 572, Issue 1, 1 November 2015, Pages 116–122
نویسندگان
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