MiR-105 inhibits gastric cancer cells metastasis, epithelial-mesenchymal transition by targeting SOX9
MiR-105 inhibits gastric cancer cells metastasis, epithelial-mesenchymal transition by targeting SOX9
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DOI：
10.26355/eurrev_201907_18429
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发表时间：
2019-07-01
影响因子：
3.3
通讯作者：
Xia, L.
中科院分区：
文献类型：
--
作者：
Shang, J-C;Yu, G-Z;Xia, L.
目的：胃癌是最常见的消化道恶性肿瘤之一，诊断时往往已是晚期。MicroRNA-105（miR-105）下调，并在多种癌症中充当肿瘤抑制因子。本研究旨在探讨miR-105和性别决定区Y-box 9（sex-determining region Y-box 9，SOX 9）在胃癌中的分子机制。患者与方法：采用Western blot方法检测E-Cadherin、N-Cadherin、Vimentin和SOX 9蛋白水平。Transwell法检测细胞的迁移和侵袭能力。结果：miR-105在胃癌组织和细胞中表达下调，抑制胃癌细胞的迁移、侵袭和上皮间质转化（EMT）。SOX 9在胃癌细胞中表达上调，与miR-105呈负相关。此外，SOX 9基因的敲低可抑制胃癌细胞的迁移、侵袭和EMT。SOX 9是miR-105的靶基因，受miR-105介导。SOX 9可逆转miR-105在细胞迁移和侵袭中的部分功能。此外，miR-105下调或SOX 9上调预测预后不良。结论：我们发现，miR-105下调，并通过结合SOX 9抑制胃癌细胞的迁移，侵袭和EMT。此外，我们证明了miR-105下调或SOX 9上调预测预后不良。新发现的miR-105/SOX 9轴为胃癌治疗提供了新的见解。
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.