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微小 RNA-212 促进食管鳞癌细胞的迁移和侵袭。

MicroRNA‑212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.

出版信息

Mol Med Rep. 2019 Oct;20(4):3633-3641. doi: 10.3892/mmr.2019.10647. Epub 2019 Sep 3.

Abstract

As a tumor‑associated microRNA (miR), miR‑212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR‑212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus‑mediated gain‑of‑function demonstrated promotion of ESCC cell migration and invasion when miR‑212 was overexpressed, and no effect on cell proliferation. miR‑212 resulted in downregulation of the expression of E‑cadherin, β‑catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)‑degrading enzymes, matrix metalloproteinase‑9 and urokinase‑type plasminogen activator. Furthermore, berberine inhibited miR‑212‑induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5‑(Tetradecyloxy)‑2‑furoic acid (TOFA; an acetyl‑CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR‑212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial‑mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR‑212.

摘要

作为一种肿瘤相关 microRNA(miR),miR-212 具有双重功能;既可以作为癌基因,也可以作为肿瘤抑制因子。有报道称,miR-212 的高表达水平与食管鳞状细胞癌(ESCC)患者的不良预后相关,但它在 ESCC 进展中的作用尚未得到探索。在本研究中,通过慢病毒介导的 gain-of-function 的体外细胞模型表明,miR-212 过表达可促进 ESCC 细胞迁移和侵袭,而对细胞增殖没有影响。miR-212 导致 E-钙黏蛋白、β-连环蛋白、波形蛋白和 Twist1 的表达下调。此外,它导致细胞外基质(ECM)降解酶、基质金属蛋白酶-9 和尿激酶型纤溶酶原激活物的水平升高。此外,小檗碱抑制了 miR-212 诱导的 ESCC 细胞迁移,而不像 PI3K 抑制剂 LY294002、雷帕霉素(mTOR 抑制剂)、5-(十四烷氧基)-2-呋喃酸(TOFA;乙酰辅酶 A 羧化酶 1 抑制剂)、二甲双胍和普萘洛尔。这些数据表明,miR-212 通过激活多个信号级联反应,并通过促进上皮间质转化和降解 ECM 来促进 ESCC 细胞的迁移和侵袭。小檗碱可能是一种针对表达高水平 miR-212 的 ESCC 患者转移的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68f/6755231/fc43c0a442c0/MMR-20-04-3633-g00.jpg

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