کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8526391 1557945 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73
چکیده انگلیسی
Our previous work has demonstrated that miR-323 enhances tumor angiogenesis in prostate cancer. In the present study, we sought to determine the function of miR-323 in prostate cancer cell growth and response to docetaxel. The effects of miR-323 overexpression on prostate cancer cell proliferation, colony formation, and tumorigenesis were examined. We also investigated the impact of miR-323 knockdown on cell cycle progression and apoptosis. Ectopic expression of miR-323 promoted cell proliferation and colony formation in vitro and xenograft tumor growth in vivo. Depletion of miR-323 arrested PC-3 prostate cancer cells at the G0/G1 phase and caused significant apoptosis, which was coupled with increased expression of p21 and cleavage of caspase-9 and caspase-3 and reduced expression of cyclin D1. Compared to PC-3 parental cells, docetaxel-resistant PC-3-DR cells had 5.6-fold higher levels of miR-323. Overexpression of miR-323 increased the 50% inhibitory concentration (IC50) value for docetaxel in PC-3 cells, while silencing of miR-323 exerted an opposite effect on PC-3-DR cells. Mechanistically, miR-323 repressed the expression of p73 in prostate cancer cells. Knockdown of p73 augmented cell proliferation and colony formation and blunted sensitivity to docetaxel in PC-3 cells. In addition, overexpression of p73 significantly suppressed cell proliferation and induced apoptosis and docetaxel sensitivity in PC-3-DR cells. In conclusion, miR-323 contributes to the aggressive phenotype of prostate cancer cells by targeting p73 and represents a potential therapeutic target for this malignancy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 97, January 2018, Pages 528-534
نویسندگان
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