title: ADAM9 functions as a promoter of gastric cancer growth which is negatively and post-transcriptionally regulated by miR-126.
abstract: 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.
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jiqi
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C527111:MIRN126 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051722:ADAM Proteins; C098339:ADAM9 protein, human