STAT3/HOTAIR Signaling Axis Regulates HNSCC Growth in an EZH2-dependent Manner
العنوان: | STAT3/HOTAIR Signaling Axis Regulates HNSCC Growth in an EZH2-dependent Manner |
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المؤلفون: | Yu Qiao, Jingxuan Yang, Shanshan Sun, Chuanqiang Wu, Yu Wang, Minghui Zhao, Xudong Wang, Xuan Zhou, Mingyang Liu, Min Li, Feng Yu, Lun Zhang, Zhaoqing Li, Chao Zhang, Yu Ren, Lingping Kong, Yuqing Zhang, Chao Jing, Xiaofeng Yao, Yansheng Wu, Wenyu Guo |
المصدر: | Clinical Cancer Research. 24:2665-2677 |
بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Antineoplastic Agents, Mice, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Cell Line, Tumor, otorhinolaryngologic diseases, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, RNA, Small Interfering, STAT3, neoplasms, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Cetuximab, biology, Squamous Cell Carcinoma of Head and Neck, Chemistry, Cell Cycle, EZH2, HOTAIR, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Disease Models, Animal, stomatognathic diseases, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, biology.protein, RNA Interference, RNA, Long Noncoding, HOX Transcript Antisense RNA, Signal Transduction, medicine.drug |
الوصف: | Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR. |
تدمد: | 1557-3265 1078-0432 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89eb7b49550e79381c323aa3511cf71fTest https://doi.org/10.1158/1078-0432.ccr-16-2248Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....89eb7b49550e79381c323aa3511cf71f |
قاعدة البيانات: | OpenAIRE |
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