ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126

A disintegrin and metalloproteinase domain 9 (ADAM9) is a membrane-anchored protein implicated in cell-cell and cell-matrix interactions, including the process of tumorigenesis. However, the role of ADAM9 in gastric cancer (GC) has not been clearly illustrated. In the present study, we found aberrant overexpression of ADAM9 in both GC tissues and cell lines. The expression of ADAM9 was significantly correlated with patient clinicopathological features including tumor size, local invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Knockdown of ADAM9 in GC SGC-7901 cells, which presented the highest ADAM9 expression among the cell lines, induced a dramatic suppression of cell proliferation along with the arrest of the cell cycle in the G0/G1 phase. Furthermore, we validated that the 3' untranslated region of ADAM9 mRNA could be bound by miR-126, a suppressor in GC, and overexpression of miR-126 significantly downregulated ADAM9 in the GC cells. In conclusion, ADAM9 functions as a tumor promoter in GC by modulating GC cell proliferation. ADAM9 could possibly be regarded as a biomarker for GC diagnosis and prevention. Moreover, as directly targeted by miR-126 in GC, ADAM9 may be a potential target for GC therapeutic treatment which warrants intensive study.