Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma Metastasis via PI3K/Akt and MEK/Erk Signaling

Molecular Therapy : the Journal of the American Society of Gene Therapy
Shule XieZhaoyu Lin

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 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (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 microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and...Continue Reading

Citations

Dec 22, 2020·Journal of Cellular and Molecular Medicine·Shanghui ZhouChenping Zhang
Jan 26, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Taheri
Feb 24, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Qing GuoYizhe Yao
Aug 10, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoting LinFeng Ye
Apr 12, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yingru LiChaobin Pan

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