近日，國(guó)際生物學(xué)期刊Cell death &disease在線發(fā)表了來(lái)自中山大學(xué)一研究小組的最新研究成果。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。
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.
