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Upregulation of lncRNA ADAMTS9-AS2 promotes salivary adenoid cystic carcinoma (SACC) metastasis via miR-143-3p-mediated regulation of PI3K/Akt and MEK/Erk signaling

ABSTRACT: Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however their potential roles in SACC are unclear. In our study, we found that ADAMTS9-AS2 was significantly upregulated in SACC patients with metastasis and SACC -LM cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2 which mainly expressed in the cytoplasm shared miRNA response elements with ITGA6. Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, thus activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2 and provides a possible application for the SACC treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117575 | GEO | 2018/07/25

REPOSITORIES: GEO

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