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MicroRNA-212 通过调控泛素特异性蛋白酶-9 抑制非小细胞肺癌的侵袭和迁移。

MicroRNA-212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin-specific protease-9.

机构信息

Cancer Institute of Integrated Taditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Department of pharmacy, The Affiliated Cangnan Hospital of Wenzhou Medical University, The People's Hospital of Cangnan, Wenzhou, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6482-6489. doi: 10.1002/jcb.27939. Epub 2018 Oct 18.

Abstract

MicroRNAs (miRNAs) play crucial roles in various biological processes, including migration, proliferation, differentiation, cell cycling, and apoptosis. Epithelial-mesenchymal transition (EMT) has been shown to be related to the capability of migration and invasion in many tumor cells. In this study, we used wound-healing assay and transwell invasion to analysis the capability of migration and invasion in non-small-cell lung carcinoma (NSCLC), respectively. The expression of ubiquitin-specific protease-9-X-linked (USP9X) and miR-212 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction and Western blot analysis was used to determine the E-cadherin and vimentin expression. Our results showed that miR-212 mimic inhibited cell migration and invasion, while miR-212 inhibitor increased cell migration and invasion. There was no significant difference between WP1130 and miR-212 mimic combined with WP1130 groups. Moreover, WP1130 inhibited the capability of the migration and invasion of NSCLC cells. Western blot analysis displayed that miR-212 mimic upregulated E-cadherin expression and downregulated vimentin expression, while miR-212 inhibitor downregulated E-cadherin and upregulated vimentin expression. These data showed that miR-212 regulated NSCLC cell invasion and migration by regulating USP9X expression. Taken together, these findings indicated that miR-212 regulated NSCLC cells migration and invasion through targeting USP9X involved in EMT.

摘要

微小 RNA(miRNA)在各种生物过程中发挥着关键作用,包括迁移、增殖、分化、细胞周期和凋亡。上皮-间充质转化(EMT)已被证明与许多肿瘤细胞的迁移和侵袭能力有关。在这项研究中,我们分别使用划痕愈合实验和 Transwell 侵袭实验分析非小细胞肺癌(NSCLC)的迁移和侵袭能力。通过定量实时聚合酶链反应确定泛素特异性蛋白酶 9-X 连锁(USP9X)和 miR-212 信使 RNA(mRNA)的表达,并用 Western blot 分析来确定 E-钙黏蛋白和波形蛋白的表达。我们的结果表明,miR-212 模拟物抑制细胞迁移和侵袭,而 miR-212 抑制剂则增加细胞迁移和侵袭。WP1130 组与 miR-212 模拟物联合 WP1130 组之间没有显著差异。此外,WP1130 抑制了 NSCLC 细胞迁移和侵袭的能力。Western blot 分析显示,miR-212 模拟物上调了 E-钙黏蛋白的表达,下调了波形蛋白的表达,而 miR-212 抑制剂则下调了 E-钙黏蛋白的表达,上调了波形蛋白的表达。这些数据表明,miR-212 通过调节 USP9X 表达来调节 NSCLC 细胞的侵袭和迁移。综上所述,这些发现表明,miR-212 通过靶向 EMT 相关的 USP9X 调节 NSCLC 细胞的迁移和侵袭。

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