近日，生物學(xué)期刊Cell death &disease在線發(fā)表了來(lái)自中山大學(xué)一研究小組的研究成果。他們通過(guò)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(guò)實(shí)驗(yàn)證明miR-34c能夠通過(guò)直接抑制原癌基因MET表達(dá)抑制鼻咽癌腫瘤生長(zhǎng)和轉(zhuǎn)移。這項(xiàng)研究對(duì)治療鼻咽癌提供了機(jī)制上的借鑒意義。

研究人員通過(guò)對(duì)NPC細(xì)胞系和病人組織樣本進(jìn)行分析發(fā)現(xiàn)，miR-34c在細(xì)胞和組織內(nèi)均發(fā)生明顯表達(dá)下調(diào)。通過(guò)在細(xì)胞系內(nèi)過(guò)量表達(dá)miR-34c發(fā)現(xiàn)，NPC細(xì)胞存活能力，集落形成，細(xì)胞遷移及侵襲能力都受到明顯抑制，同時(shí)體內(nèi)實(shí)驗(yàn)也證明miR-34c過(guò)表達(dá)能夠抑制腫瘤生長(zhǎng)及肺轉(zhuǎn)移。研究人員通過(guò)實(shí)驗(yàn)發(fā)現(xiàn)miR-34c能夠直接作用于原癌基因MET，miR-34c過(guò)表達(dá)能夠明顯降低MET的mRNA和蛋白水平。在細(xì)胞內(nèi)敲低MET能夠抑制NPC細(xì)胞增殖，遷移和侵襲，同時(shí)恢復(fù)MET表達(dá)能夠改變miR-34c對(duì)腫瘤細(xì)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(fù)miR-34c表達(dá)的化學(xué)分子。

綜上所述，該項(xiàng)研究發(fā)現(xiàn)miR-34c能夠通過(guò)影響MET表達(dá)抑制鼻咽癌腫瘤生長(zhǎng)和轉(zhuǎn)移,關(guān)于miR-34c/MET新通路的發(fā)現(xiàn)或許可以為進(jìn)一步研究NPC發(fā)展機(jī)制以及開(kāi)發(fā)治療NPC的藥物提供重要借鑒意義。

原文標(biāo)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.