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

被引:47
|
作者
Li, Yingru [4 ,5 ]
Wan, Quan [1 ,2 ]
Wang, Weiwei [3 ]
Mai, Lianxi [1 ,2 ]
Sha, Liujuan [1 ]
Mashrah, Mubarak [1 ,2 ]
Lin, Zhaoyu [1 ,2 ]
Pan, Chaobin [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oral & Maxillofacial Surg, Guangzhou 510120, Guangdong, Peoples R China
[3] Zibo Ctr Hosp, Dept Stomatol, Zibo 255000, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Gastroenterol Hernia & Abdominal Wall Surg, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Tongue squamous cell carcinoma; lncRNA; miR-600; EZH2; ADAMTS9-AS2; LONG NONCODING RNA; CANCER DEVELOPMENT; TARGETING EZH2; LUNG-CANCER; INVASION; METASTASIS; CONTRIBUTES; POLYCOMB; PATHWAY; GROWTH;
D O I
10.1016/j.biopha.2019.108719
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-beta 1 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.
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页数:9
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