Wang Junqing, Zhou Yunyun, Fei Xiaochun, Chen Xuehua, Yan Jiqi, Liu Bingya, Zhu Zhenggang
Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Department of Data Science, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Oncol Rep. 2017 Apr;37(4):2033-2040. doi: 10.3892/or.2017.5460. Epub 2017 Feb 16.
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.
解整合素金属蛋白酶结构域9（ADAM9）是一种膜锚定蛋白，参与细胞间和细胞与基质的相互作用，包括肿瘤发生过程。然而，ADAM9在胃癌（GC）中的作用尚未得到明确阐释。在本研究中，我们发现ADAM9在GC组织和细胞系中均存在异常过表达。ADAM9的表达与患者的临床病理特征显著相关，包括肿瘤大小、局部浸润、淋巴结转移和肿瘤-淋巴结-转移（TNM）分期。在细胞系中ADAM9表达最高的GC SGC-7901细胞中敲低ADAM9，可显著抑制细胞增殖，并使细胞周期停滞在G0/G1期。此外，我们证实ADAM9 mRNA的3'非翻译区可被GC中的抑制因子miR-126结合，miR-126的过表达可显著下调GC细胞中ADAM9的表达。总之，ADAM9通过调节GC细胞增殖在GC中发挥肿瘤促进作用。ADAM9可能被视为GC诊断和预防的生物标志物。此外，由于在GC中被miR-126直接靶向，ADAM9可能是GC治疗的潜在靶点，值得深入研究。
