生物资讯

中国科学家发现抑制鼻咽癌生长转移新机制

作者:admin 来源:Cell death&disease 发布时间: 2015-01-30 15:23  浏览次数:
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 Cell death&disease:中国科学家发现抑制鼻咽癌生长转移新机制

近日,国际生物学期刊Cell death &disease在线发表了来自中山大学一研究小组的最新研究成果。他们通过基因芯片分析发现miR-34c在鼻咽癌(NPC)中发生下调,并通过实验证明miR-34c能够通过直接抑制原癌基因MET表达抑制鼻咽癌肿瘤生长和转移。这项研究对治疗鼻咽癌提供了机制上的借鉴意义。

研究人员通过对NPC细胞系和病人组织样本进行分析发现,miR-34c在细胞和组织内均发生明显表达下调。通过在细胞系内过量表达miR-34c发现,NPC细胞存活能力,集落形成,细胞迁移及侵袭能力都受到明显抑制,同时体内实验也证明miR-34c过表达能够抑制肿瘤生长及肺转移。研究人员通过实验发现miR-34c能够直接作用于原癌基因MET,miR-34c过表达能够明显降低MET的mRNA和蛋白水平。在细胞内敲低MET能够抑制NPC细胞增殖,迁移和侵袭,同时恢复MET表达能够改变miR-34c对肿瘤细胞的抑制效应。除此之外,研究人员还发现了一种能够恢复miR-34c表达的化学分子。

综上所述,该项研究发现miR-34c能够通过影响MET表达抑制鼻咽癌肿瘤生长和转移,关于miR-34c/MET新通路的发现或许可以为进一步研究NPC发展机制以及开发治疗NPC的药物提供重要借鉴意义。

原文标题:MiR-34c suppresses tumor growth and metastasis in nasopharyngeal carcinoma by targeting MET

Our previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro, and inhibited xenograft tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, Western Blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment.

 

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