کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5529335 1401693 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original articleUpregulated expression of Nucleostemin/GNL3 is associated with poor prognosis and Sorafenib Resistance in Hepatocellular Carcinoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original articleUpregulated expression of Nucleostemin/GNL3 is associated with poor prognosis and Sorafenib Resistance in Hepatocellular Carcinoma
چکیده انگلیسی

Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pathology - Research and Practice - Volume 213, Issue 6, June 2017, Pages 688-697
نویسندگان
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