کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8716260 1587880 2018 35 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Tumor-Promoting Role of TRIP4 in Melanoma Progression and its Involvement in Response to BRAF-Targeted Therapy
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
The Tumor-Promoting Role of TRIP4 in Melanoma Progression and its Involvement in Response to BRAF-Targeted Therapy
چکیده انگلیسی
TRIP4 was identified as having a proliferation promoting effect in melanoma cells based on small interfering RNA library screening, however, its precise function in melanoma progression is completely unknown. Here, we explored the carcinogenic role of TRIP4 in melanoma. The high expression of TRIP4 was observed in human melanoma cells and tissues. Its knockdown suppressed melanoma progression in vitro and in vivo, including melanoma cell proliferation, migration, and invasion inhibition and apoptosis induction. Further mechanistic analysis showed that TRIP4 promoted melanoma growth through modulation of COX-2 and iNOS expression partially by activating NF-κB signaling indirectly and partially by the direct anchoring of itself at COX-2 and iNOS promoter via synergy with p300. TRIP4 was confirmed to regulate the sensitivity to anti-BRAF targeted agents in BRAF-mutant human melanoma cells and xenografts. In addition, clinical data showed that high expression of TRIP4 was positively correlated with increased expression of COX-2 and iNOS and predicted poor prognosis in a cohort of 100 melanoma patients. Collectively, these results show a pro-tumorigenic role of TRIP4, provide an insight into the mechanism of TRIP4 as a candidate therapeutic target, and suggest the potential of TRIP4 and BRAF dual targeting as an effective therapeutic strategy for melanoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 1, January 2018, Pages 159-170
نویسندگان
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