miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway.
miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway.
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miR-135a通过靶向FAK通路抑制肿瘤转移和血管生成
DOI：
10.18632/oncotarget.16098
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发表时间：
2017-05-09
期刊：
影响因子：
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通讯作者：
Li F
中科院分区：
文献类型：
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作者：
Cheng Z;Liu F;Zhang H;Li X;Li Y;Li J;Liu F;Cao Y;Cao L;Li F
肿瘤转移一直是胃癌患者复发和死亡的主要原因。在这里，我们通过分析 microRNA 阵列发现 miR-135a 在转移细胞系中的表达与其亲代细胞系相比有所降低。进一步的结果表明，miR-135a在大多数人胃癌组织和细胞系中表达下调。 miR-135a 表达降低与 TNM 分期和较差的生存率相关。此外，在胃癌细胞中恢复miR-135a可通过靶向粘着斑激酶（FAK）途径明显抑制肿瘤生长、迁移、侵袭和血管生成。生物信息学分析和分子实验进一步证明miR-135a是抑癌基因p53的新型下游基因。用 FAK 抑制剂阻断 FAK 还可以通过诱导 p53 增强 miR-135a 表达。综上所述，本研究揭示了miR-135a在胃癌中的表达和功能，并揭示了miR-135a新的调控机制。
Tumor metastasis has been the major cause of recurrence and death in patients with gastric cancer. Here, we find miR-135a has a decreased expression in the metastatic cell lines compared with its parental cell lines by analyzing microRNA array. Further results show that miR-135a is downregulated in the majority of human gastric cancer tissues and cell lines. Decreased expression of miR-135a is associated with TNM stage and poor survival. Besides, regaining miR-135a in gastric cancer cells obviously inhibits tumor growth, migration, invasion and angiogenesis by targeting focal adhesion kinase (FAK) pathway. Bioinformatics analysis and molecular experiments further prove that miR-135a is a novel downstream gene of tumor suppressor p53. Blocking FAK with its inhibitor can also enhance miR-135a expression through inducing p53. In summary, this study reveals the expression and function of miR-135a in gastric cancer and uncovers a novel regulatory mechanism of miR-135a.