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LINC00319 acts as a microRNA-335-5p sponge to accelerate tumor growth and metastasis in gastric cancer by up-regulating ADCY3.

Gastric cancer (GC) is one of the most common cancers in the world and remains a heavy burden of health worldwide. Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues and has been identified to be a new molecular target of GC. Long non-coding RNAs (lncRNAs) have substantial influence on tumorigenesis and progression of tumors by binding to microRNAs (miRNAs). Therefore, this study is to clarify the mechanism by which LINC00319 sponges miR-335-5p to influence development of GC. Initially, microarray analysis identified GC-related differentially expressed LINC00319 and ADCY3 for this study. The interaction was confirmed that LINC00319 interacted with miR-335-5p to regulate ADCY3. Next, SGC-7901 cells presenting with the lowest LINC00319 expression and the highest miR-335-5p expression were transfected with LINC00319, miR-335-5p inhibitor or ADCY3 vector to examine their roles in growth and metastasis of GC cells, which was further ascertained by in vivo experiments. LINC00319 was up-regulated, and miR-335-5p was down-regulated in GC cells. LINC00319 overexpression, miR-335-5p inhibitor or ADCY3 overexpression was shown to significantly elevate the expression of CDK4 and MTA1, decrease that of GAS1, and promote tumor growth and metastasis by increasing proliferation, migration and reducing cell apoptosis. Importantly, it was found that overexpressed miR-335-5p exerted its tumor suppressive role in GC through down-regulating ADCY3. Collectively, LINC00319 expedited growth and metastasis of GC by up-regulating miR-335-5p-mediated ADCY3.