miR-105 通过靶向 SOX9 抑制胃癌细胞转移和上皮-间充质转化。
MiR-105 inhibits gastric cancer cells metastasis, epithelial-mesenchymal transition by targeting SOX9.
机构信息
Department of General, the First Affiliated Hospital of Jiamusi University, Jiamusi, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6160-6169. doi: 10.26355/eurrev_201907_18429.
OBJECTIVE
Gastric cancer is one of the most common gastrointestinal malignancy, which is often diagnosed at an advanced stage. MicroRNA-105 (miR-105) was downregulated and acts as a tumor suppressor in various cancers. The purpose of this study was to explore the molecular mechanisms of miR-105 and sex-determining region Y-box 9 (SOX9) in gastric cancer.
PATIENTS AND METHODS
Western blot was performed to display the protein level of E-Cadherin, N-Cadherin, Vimentin and SOX9. Transwell assay was utilized to measure the capacity of migration and invasion. We employed the Luciferase reporter assay to determine miR-105 targeting to SOX9 in gastric cancer.
RESULTS
MiR-105 was downregulated in gastric cancer tissues and cells; it suppressed gastric cancer cell migration, invasion and epithelial-mesenchymal transition (EMT) in gastric cancer. SOX9 was upregulated in gastric cancer cells and had a negative correlation with miR-105. Moreover, the knockdown of SOX9 could inhibit gastric cancer cell migration, invasion and EMT. Furthermore, SOX9 was a target gene of miR-105 and mediated by miR-105. SOX9 could reverse the partial function of miR-105 on cell migration and invasion. In addition, miR-105 downregulation or SOX9 upregulation predicted a poor prognosis.
CONCLUSIONS
We showed that miR-105 was downregulated and inhibited cell migration, invasion and EMT in gastric cancer by binding to SOX9. In addition, we demonstrated that miR-105 downregulation or SOX9 upregulation predicted a poor prognosis. The newly discoverable miR-105/SOX9 axis provides novel insight into gastric cancer treatment.
目的
胃癌是最常见的胃肠道恶性肿瘤之一，通常在晚期诊断。microRNA-105（miR-105）在各种癌症中下调并作为肿瘤抑制因子发挥作用。本研究旨在探讨 miR-105 和性别决定区 Y 框 9（SOX9）在胃癌中的分子机制。
患者和方法
采用 Western blot 法显示 E-钙黏蛋白、N-钙黏蛋白、波形蛋白和 SOX9 的蛋白水平。采用 Transwell assay 测定迁移和侵袭能力。我们采用荧光素酶报告基因 assay 确定 miR-105 在胃癌中对 SOX9 的靶向作用。
结果
miR-105 在胃癌组织和细胞中下调；它抑制胃癌细胞迁移、侵袭和上皮-间充质转化（EMT）。SOX9 在胃癌细胞中上调，与 miR-105 呈负相关。此外，SOX9 的敲低可抑制胃癌细胞迁移、侵袭和 EMT。此外，SOX9 是 miR-105 的靶基因，受 miR-105 介导。SOX9 可以逆转 miR-105 对细胞迁移和侵袭的部分功能。此外，miR-105 下调或 SOX9 上调预示预后不良。
结论
我们表明，miR-105 通过与 SOX9 结合而下调，抑制胃癌细胞迁移、侵袭和 EMT。此外，我们证明 miR-105 下调或 SOX9 上调预示预后不良。新发现的 miR-105/SOX9 轴为胃癌治疗提供了新的见解。
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