کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8715938 | 1587875 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dual Role of EZH2 in Cutaneous Anaplastic Large Cell Lymphoma: Promoting Tumor Cell Survival and Regulating Tumor Microenvironment
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کلمات کلیدی
CXCR3Histone H3 lysine 27 trimethylationLCTCTCLPRC2H3K27me3TXNIPCXCL10EZH2ROS - ROSLyP - خواستنMycosis fungoides - قارچ MycosisCutaneous T-cell lymphoma - لنفوم پوستی TLymphomatoid papulosis - پاپولوز لنفوموئیدthioredoxin-interacting protein - پروتئین تعامل کننده تیورودکسینpolycomb repressive complex 2 - پیچک سرکوبگر پلی کامب 2Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Dual Role of EZH2 in Cutaneous Anaplastic Large Cell Lymphoma: Promoting Tumor Cell Survival and Regulating Tumor Microenvironment Dual Role of EZH2 in Cutaneous Anaplastic Large Cell Lymphoma: Promoting Tumor Cell Survival and Regulating Tumor Microenvironment](/preview/png/8715938.png)
چکیده انگلیسی
Primary cutaneous anaplastic T-cell lymphoma, characterized by the CD30+ anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma. Little is known about the mechanisms of disease progression. Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 that mediates histone H3 lysine 27 trimethylation, is overexpressed in CD30+ anaplastic cells in primary cutaneous anaplastic T-cell lymphoma and large-cell transformed cutaneous T-cell lymphoma. Silencing EZH2 or inhibiting its histone methyltransferase activity conferred increased apoptosis and G1 cell-cycle arrest in primary cutaneous anaplastic T-cell lymphoma cells in vitro and a xenograft model in vivo. This was mediated by the de-repression of thioredoxin-interacting protein, a major redox control molecule, and consequent formation of reactive oxygen species. Silencing thioredoxin-interacting protein abrogated reactive oxygen species accumulation in EZH2 suppressed cells and rescued cell growth disadvantage. Moreover, EZH2 suppression de-repressed C-X-C motif chemokine ligand 10 and facilitated the recruitment of effector CD4+ and CD8+ T cells into the tumor microenvironment via a C-X-C motif chemokine ligand 10/receptor 3 interaction. These results demonstrate a dual role for polycomb repressive complex 2-mediated epigenetic silencing in tumor progression and antitumor immunity in primary cutaneous anaplastic T-cell lymphoma, and provide a rationale for the pharmacologic inhibition of EZH2 activity in large-cell transformed cutaneous T-cell lymphoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 5, May 2018, Pages 1126-1136
Journal: Journal of Investigative Dermatology - Volume 138, Issue 5, May 2018, Pages 1126-1136
نویسندگان
Shengguo Yi, Jingru Sun, Lei Qiu, Wenjing Fu, Anqi Wang, Xiaoqing Liu, Yong Yang, Marshall E. Kadin, Ping Tu, Yang Wang,