کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8715852 | 1587873 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma
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کلمات کلیدی
ChIP-SeqCTDGSEAGI50Small interfering RNA - RNA تداخل کوچکsiRNA - siRNASER - برای بودنGene Set Enrichment Analysis - تجزیه و تحلیل غنی سازی مجموعه ژنیchromatin immunoprecipitation sequencing - توالی آمپول اکسایش کروماتینcarboxy-terminal domain - دامنه کربوکسی-ترمینالSerine - سرینsuper-enhancer - فوق العاده تقویت کنندهPol II - پل دومpolymerase II - پلیمراز II
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma](/preview/png/8715852.png)
چکیده انگلیسی
Cutaneous melanoma is an aggressive tumor that accounts for most skin cancer deaths. Among the physiological barriers against therapeutic success is a strong survival program driven by genes such as MITF that specify melanocyte identity, a phenomenon known in melanoma biology as lineage dependency. MITF overexpression is occasionally explained by gene amplification, but here we show that super-enhancers are also important determinants of MITF overexpression in some melanoma cell lines and tumors. Although compounds that directly inhibit MITF are unavailable, a covalent CDK7 inhibitor, THZ1, has recently been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We also show that melanoma cells are highly sensitive to CDK7 inhibition both in vitro and in vivo and that THZ1 can dismantle the super-enhancer apparatus at MITF and SOX10 in some cell lines, thereby extinguishing their intracellular levels. Our results show a dimension to MITF regulation in melanoma cells and point to CDK7 inhibition as a potential strategy to deprive oncogenic transcription and suppress tumor growth in melanoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 7, July 2018, Pages 1582-1590
Journal: Journal of Investigative Dermatology - Volume 138, Issue 7, July 2018, Pages 1582-1590
نویسندگان
Philip Eliades, Brian J. Abraham, Zhenyu Ji, David M. Miller, Camilla L. Christensen, Nicholas Kwiatkowski, Raj Kumar, Ching Ni Njauw, Michael Taylor, Benchun Miao, Tinghu Zhang, Kwok-Kin Wong, Nathanael S. Gray, Richard A. Young, Hensin Tsao,