miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer.

miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer.
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DOI:
10.1371/journal.pone.0072662
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
He ZM
He ZM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Deng M;Tang HL;Lu XH;Liu MY;Lu XM;Gu YX;Liu JF;He ZM

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在以前的研究中,miR-26a在癌细胞中的作用似乎存在争议。到目前为止,miR-26a在胃癌中的作用仍不明确。在本研究中,我们发现miR-26a在胃癌组织和细胞系中表达显著下调,其表达水平与胃癌的淋巴转移和临床分期、总生存期和无复制酶生存期有关。我们还发现异位表达miR-26a在体内外抑制了GC细胞的增殖和胃癌的转移。我们进一步确定了miR-26a抑制胃癌生长和转移的新机制。通过荧光素酶活性测定和Western印迹分析,证明Fgf9是miR-26a的直接靶点。在miR-26a表达细胞中过表达Fgf9可以修复miR-26a的侵袭和生长缺陷。此外,miR-26a在胃癌中的表达与FGF9蛋白水平呈负相关。综上所述,我们的数据表明miR-26a在胃癌的发生和发展中起着肿瘤抑制因子的作用,并有望成为胃癌的预后生物标志物和潜在的治疗靶点。
The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.
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