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长链非编码RNA LINC01296通过对KLF2的表观遗传抑制促进食管鳞状细胞癌细胞的增殖和侵袭。

Long non-coding RNA LINC01296 promotes esophageal squamous cell carcinoma cell proliferation and invasion by epigenetic suppression of KLF2.

作者信息

Wang Luming, Meng Di, Wang Yiqing, Hu Jian

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou 310003, Zhejiang Province, China.

出版信息

Am J Cancer Res. 2018 Oct 1;8(10):2020-2029. eCollection 2018.

Abstract

Dysregulated long non-coding RNAs (lncRNAs) are found in many types of tumors, including esophageal squamous cell carcinoma (ESCC); however, the pattern of expression and function of LINC01296 in esophageal squamous cell carcinoma are unknown. In the current study we showed that LINC01296 expression is significantly higher in ESCC tissues when compared with corresponding adjacent normal tissues. Higher LINC01296 expression was associated with lymph node metastasis, TNM stage, and worse overall survival rate in ESCC patients. Furthermore, functional assays demonstrated that knockdown of LINC01296 inhibited ESCC cell proliferation, colony formation, migration, and invasiveness. Moreover, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays demonstrated that LINC01296 promotes cell proliferation and invasion by epigenetic suppression of KLF2 expression via an interaction with EZH2 in ESCC cells. We also demonstrated that knockdown of LINC01296 inhibited cell growth and up-regulated KLF2 expression . These results indicate that LINC01296 acts as an oncogene and may serve as a potential target in ESCC treatment.

摘要

失调的长链非编码RNA(lncRNAs)在包括食管鳞状细胞癌(ESCC)在内的多种肿瘤类型中均有发现;然而,LINC01296在食管鳞状细胞癌中的表达模式和功能尚不清楚。在本研究中,我们发现与相应的癌旁正常组织相比,LINC01296在ESCC组织中的表达显著更高。LINC01296的高表达与ESCC患者的淋巴结转移、TNM分期及较差的总生存率相关。此外,功能分析表明,敲低LINC01296可抑制ESCC细胞增殖、集落形成、迁移及侵袭。而且,RNA免疫沉淀(RIP)和染色质免疫沉淀(ChIP)分析表明,在ESCC细胞中,LINC01296通过与EZH2相互作用对KLF2表达进行表观遗传抑制,从而促进细胞增殖和侵袭。我们还证明,敲低LINC01296可抑制细胞生长并上调KLF2表达。这些结果表明,LINC01296作为一种癌基因,可能成为ESCC治疗的潜在靶点。

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