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微小RNA-144通过调控c-Met表达抑制葡萄膜黑色素瘤细胞的增殖和侵袭。

MiR-144 Inhibits Uveal Melanoma Cell Proliferation and Invasion by Regulating c-Met Expression.

作者信息

Sun Lei, Bian Guangqing, Meng ZhaoJun, Dang Guangfu, Shi DeJing, Mi Shuyong

机构信息

Department of Ophthalmology, The Fourth Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.

Department of Ophthalmology, Shandong Provincial Qianfoshan Hospital, Jinan 250000, Shandong, China.

出版信息

PLoS One. 2015 May 11;10(5):e0124428. doi: 10.1371/journal.pone.0124428. eCollection 2015.

Abstract

MicroRNAs (miRNAs) are a group endogenous small non-coding RNAs that inhibit protein translation through binding to specific target mRNAs. Recent studies have demonstrated that miRNAs are implicated in the development of cancer. However, the role of miR-144 in uveal melanoma metastasis remains largely unknown. MiR-144 was downregulated in both uveal melanoma cells and tissues. Transfection of miR-144 mimic into uveal melanoma cells led to a decrease in cell growth and invasion. After identification of two putative miR-144 binding sites within the 3' UTR of the human c-Met mRNA, miR-144 was proved to inhibit the luciferase activity inMUM-2B cells with a luciferase reporter construct containing the binding sites. In addition, the expression of c-Met protein was inhibited by miR-144. Furthermore, c-Met-mediated cell proliferation and invasion were inhibited by restoration of miR-144 in uveal melanoma cells. In conclusion, miR-144 acts as a tumor suppressor in uveal melanoma, through inhibiting cell proliferation and migration. miR-144 might serve as a potential therapeutic target in uveal melanoma patients.

摘要

微小RNA(miRNA)是一类内源性小非编码RNA,通过与特定靶mRNA结合来抑制蛋白质翻译。最近的研究表明,miRNA与癌症的发生发展有关。然而,miR-144在葡萄膜黑色素瘤转移中的作用仍 largely未知。miR-144在葡萄膜黑色素瘤细胞和组织中均下调。将miR-144模拟物转染到葡萄膜黑色素瘤细胞中导致细胞生长和侵袭减少。在鉴定出人c-Met mRNA的3'UTR内的两个假定的miR-144结合位点后,用含有这些结合位点的荧光素酶报告构建体证明miR-144在MUM-2B细胞中抑制荧光素酶活性。此外,miR-144抑制c-Met蛋白的表达。此外,通过在葡萄膜黑色素瘤细胞中恢复miR-144来抑制c-Met介导的细胞增殖和侵袭。总之,miR-144通过抑制细胞增殖和迁移在葡萄膜黑色素瘤中起肿瘤抑制作用。miR-144可能作为葡萄膜黑色素瘤患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c72/4427317/24840bb474ea/pone.0124428.g001.jpg

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