近日，國際生物學期刊Cell death &disease在線發(fā)表了來自中山大學一研究小組的最新研究成果。他們通過基因芯片分析發(fā)現(xiàn)miR-34c在鼻咽癌(NPC)中發(fā)生下調(diào)，并通過實驗證明miR-34c能夠通過直接抑制原癌基因MET表達抑制鼻咽癌腫瘤生長和轉(zhuǎn)移。這項研究對治療鼻咽癌提供了機制上的借鑒意義。
研究人員通過對NPC細胞系和病人組織樣本進行分析發(fā)現(xiàn)，miR-34c在細胞和組織內(nèi)均發(fā)生明顯表達下調(diào)。通過在細胞系內(nèi)過量表達miR-34c發(fā)現(xiàn)，NPC細胞存活能力，集落形成，細胞遷移及侵襲能力都受到明顯抑制，同時體內(nèi)實驗也證明miR-34c過表達能夠抑制腫瘤生長及肺轉(zhuǎn)移。研究人員通過實驗發(fā)現(xiàn)miR-34c能夠直接作用于原癌基因MET，miR-34c過表達能夠明顯降低MET的mRNA和蛋白水平。在細胞內(nèi)敲低MET能夠抑制NPC細胞增殖，遷移和侵襲，同時恢復MET表達能夠改變miR-34c對腫瘤細胞的抑制效應(yīng)。除此之外，研究人員還發(fā)現(xiàn)了一種能夠恢復miR-34c表達的化學分子。
綜上所述，該項研究發(fā)現(xiàn)miR-34c能夠通過影響MET表達抑制鼻咽癌腫瘤生長和轉(zhuǎn)移,關(guān)于miR-34c/MET新通路的發(fā)現(xiàn)或許可以為進一步研究NPC發(fā)展機制以及開發(fā)治療NPC的藥物提供重要借鑒意義。
原文標題：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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