H3K27ac促进lncRNA OIP5-AS1的表达进而诱导食管鳞癌放射抵抗的产生  

Promotion of OIP5-AS1 expression by H3K27ac-induced radioresistance in esophageal squamous carcinoma

作　　者：王绩钊 刘颖[2] 张升阳 张嘉伟 屈航英 付军科[1] 张广健[1] 张明鑫 张晓智[6] WANG Jizhao;LIU Ying;ZHANG Shengyang;ZHANG Jiawei;QU Hangying;FU Junke;ZHANG Guangjian;ZHANG Mingxin;ZHANG Xiaozhi(Department of Thoracic Surgery,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Oncology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Baoji Jintai Hospital,Baoji 721400;Shaanxi University of Chinese Medicine,Xianyang 712046;Department of Gastroenterology,The First Affiliated Hospital of Xi’an Medical College,Xi’an 710077;Department of Radiation Oncology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院胸外科,陕西西安710061 [2]西安交通大学第一附属医院肿瘤内科,陕西西安710061 [3]宝鸡金台医院,陕西宝鸡721400 [4]陕西中医药大学,陕西咸阳712046 [5]西安医学院第一附属医院消化内科,陕西西安710077 [6]西安交通大学第一附属医院放疗科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2020年第5期639-644,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81773239);陕西省重点研发计划重点资助项目(No.2018ZDXM-SF-043);陕西省自然科学基金资助项目(2019JM-559);西安交大一附院院基金资助项目(2018MS-23)。

摘　　要：目的本研究旨在探索放射相关H3组蛋白修饰调控OIP5-AS1的分子机制,从而为逆转食管鳞癌放射抵抗提供依据。方法本研究纳入137例西安医学院第一附属医院食管鳞癌患者标本。qRT-PCR及Western blotting检测目的基因的表达。划痕实验及CCK8实验检测细胞迁移及增殖能力。应用ChIP检测OIP5-AS1与H3K27ac的结合情况。结果OIP5-AS1在食管癌放疗抵抗患者中高表达;且促进食管癌抵抗细胞的增殖及转移能力。H3K27ac在食管癌放射抵抗细胞中高表达,且富集于OIP5-AS1的启动子区域。CBP在食管癌放射抵抗细胞中高表达;其抑制剂C646可明显抑制H3K27ac在OIP5-AS1启动子区域的富集。结论OIP5-AS1参与调控食管鳞癌放射抵抗。CBP通过促进H3K27ac与OIP5-AS1的结合,进而激活OIP5-AS1的表达,从而促进放射抵抗的产生。Objective Our study aims to investigate the radiation associated H3 modification in regulating OIP5-AS1 to lay foundation for developing therapeutic targets on reversing radiation resistance of esophageal squamous carcinoma.Methods We recruited 137 ESCC patients from The First Affiliated Hospital of Xi’an Medical College.qRT-PCR and Western blotting were used for detecting the expressions of target genes.Wound healing assay and CCK8 assay were used to detect the migration and proliferation abilities.ChIP assay was used to detect the interaction between OIP5-AS1 and H3K27ac.Results OIP5-AS1 was highly expressed in ESCC radiation resistant patients and promoted the migration and proliferation abilities of ESCC radiation resistant cells.H3K27ac was activated in ESCC radiation resistant cells and was enriched in the promoter region of OIP5-AS1.CBP was upregulated in ESCC radiation resistant cells;its inhibitor,C646,could suppress the enrichment of H3K27ac in the promoter region of OIP5-AS1.Conclusion OIP5-AS1 regulated radioresistance in ESCC.CBP promoted the interaction between H3K27ac and OIP5-AS1,thereby activating the expression of OIP5-AS1 and resulting in radioresistance.

关 键 词：食管鳞癌 放射抵抗 OIP5-AS1 H3K27ac CBP 

分 类 号：R735.1[医药卫生—肿瘤]