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长链非编码 RNA ADAMTS9-AS2 通过 miR-600/EZH2 轴促进舌鳞癌细胞的增殖、迁移和 EMT。

LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis.

机构信息

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Gastroenterology, Hernia and Abdominal Wall Surgery, The sixth affiliated Hospital, Sun Yat_Sen University, Guangzhou, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.

出版信息

Biomed Pharmacother. 2019 Apr;112:108719. doi: 10.1016/j.biopha.2019.108719. Epub 2019 Feb 27.

Abstract

Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in tongue squamous cell carcinoma (TSCC) is attracting increasing attention. In the present study, we identify a key lncRNA regulating TSCC metastasis and investigated the underlying mechanism. Our results indicate that the lncRNA ADAMTS9-AS2 is most significantly upregulated in TSCC tissues from patients with lymph node metastasis and is closely associated with poor prognosis. Furthermore, ADAMTS9-AS2 knockdown in TSCC cells leads to a inhibition of cell migration and invasion and reverses TGF-β1 induced EMT. ADAMTS9-AS2 knockdown also inhibits TSCC cell growth in vitro and in vivo. In addition, we show that ADAMTS9-AS2 is a cytoplasmic lncRNA that shares the miRNA response elements (MREs) of miR-600 with EZH2, which is confirmed by a luciferase reporter assay and AGO2-dependent RNA immunoprecipitation (RIP). In summary, our results demonstrate an explicit oncogenic role of ADAMTS9-AS2 in TSCC tumorigenesis via competition with miR-600, suggesting a new regulatory mechanism of ADAMTS9-AS2 and providing a potential therapeutic target for TSCC patients.

摘要

长链非编码 RNA(lncRNA)是一种非编码 RNA 转录本,其特征是缺乏蛋白质编码能力。lncRNA 在舌鳞状细胞癌(TSCC)中的重要作用正引起越来越多的关注。在本研究中,我们鉴定了一种调节 TSCC 转移的关键 lncRNA,并研究了其潜在的机制。我们的结果表明,lncRNA ADAMTS9-AS2 在有淋巴结转移的 TSCC 组织中表达上调最为显著,与不良预后密切相关。此外,ADAMTS9-AS2 在 TSCC 细胞中的敲低导致细胞迁移和侵袭的抑制,并逆转 TGF-β1 诱导的 EMT。ADAMTS9-AS2 敲低还抑制了 TSCC 细胞在体外和体内的生长。此外,我们表明 ADAMTS9-AS2 是一种细胞质 lncRNA,与 EZH2 共享 miR-600 的 miRNA 反应元件(MREs),这通过荧光素酶报告基因检测和AGO2 依赖性 RNA 免疫沉淀(RIP)得到证实。总之,我们的结果表明,ADAMTS9-AS2 在 TSCC 肿瘤发生中通过与 miR-600 竞争发挥明确的致癌作用,提示 ADAMTS9-AS2 的新调节机制,并为 TSCC 患者提供了一个潜在的治疗靶点。

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