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

Affiliation

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. Electronic address: [Email]

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.

Keywords

ADAMTS9-AS2,EZH2,Tongue squamous cell carcinoma,lncRNA,miR-600,

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