کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8437348 | 1546868 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Roles of Alternative RNA Splicing of the Bif-1 Gene by SRRM4 During the Development of Treatment-induced Neuroendocrine Prostate Cancer
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کلمات کلیدی
CPTNeuroendocrine prostate cancerN-BARPCA - PCARNA in situ hybridization - RNA در محل hybridizationProstate adenocarcinoma - آدنوکارسینوم پروستاتBax - باکسBif-1 - بیف 1Apoptosis - خزان یاختهایProstate cancer - سرطان پروستاتneuroendocrine - عصبی عضلانیBcl-2 Associated X protein - پروتئین Bcl-2 Associated XAlternative RNA splicing - پلاسر RNA جایگزینSmall cell neuroendocrine carcinoma - کارسینوم عصبی عصبی سلولی کوچکcamptothecin - کامپتوتسین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that becomes more prevalent when hormonal therapy, chemotherapy, or radiation therapy is applied to patients with metastatic prostate adenocarcinoma (AdPC). How AdPC cells survive these anti-cancer therapies and progress into t-NEPC remains unclear. By comparing the whole transcriptomes between AdPC and t-NEPC, we identified Bif-1, an apoptosis-associated gene, which undergoes alternative RNA splicing in t-NEPC. We found that while Bif-1a is the predominant variant of the Bif-1 gene in AdPC, two neural-specific variants, Bif-1b and Bif-1c, are highly expressed in t-NEPC patients, patient derived xenografts, and cell models. The neural-specific RNA splicing factor, SRRM4, promotes Bif-1b and Bif-1c splicing, and the expression of SRRM4 in tumors is strongly associated with Bif-1b/-1c levels. Furthermore, we showed that Bif-1a is pro-apoptotic, while Bif-1b and Bif-1c are anti-apoptotic in PCa cells under camptothecin and UV light irritation treatments. Taken together, our data indicate that SRRM4 regulates alternative RNA splicing of the Bif-1 gene that enables PCa cells resistant to apoptotic stimuli under anti-cancer therapies, and may contribute to AdPC progression into t-NEPC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: EBioMedicine - Volume 31, May 2018, Pages 267-275
Journal: EBioMedicine - Volume 31, May 2018, Pages 267-275
نویسندگان
Yu Gan, Yinan Li, Zhi Long, Ahn R. Lee, Ning Xie, Jessica M. Lovnicki, Yuxin Tang, Xiang Chen, Jiaoti Huang, Xuesen Dong,