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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.

DOI:10.26355/eurrev_201907_18429
PMID:31364116
Abstract

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.

摘要

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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