來自廈門大學(xué)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)部的研究人員在腫瘤學(xué)研究權(quán)威雜志《癌基因》（Oncogene）上發(fā)表研究論文“Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophin” 。
文章的通訊作者是金光輝副教授和華先欣講座教授,，其實驗室主要研究方向為抑癌基因轉(zhuǎn)錄調(diào)控與疾病發(fā)生關(guān)系,，尤其在新發(fā)現(xiàn)的抑癌基因Men1及其編碼蛋白menin的生物學(xué)功能方面進(jìn)行了系統(tǒng),、深入的研究,。
有關(guān)基因表達(dá)沉默的表觀遺傳調(diào)控體系的建立和維持是決定細(xì)胞表型,、分化和功能特化的重要分子基礎(chǔ),。以往的研究表明，抑癌基因MEN1及其編碼蛋白menin通過與MLLs等組蛋白甲基化修飾酶相互作用而調(diào)節(jié)H3K4等正性組蛋白甲基化修飾,，但是menin是否參與其他組蛋白修飾尚不清楚,。課題組通過深入研究，首次證明了menin與Polycomb家族共同介導(dǎo)的H3K27組蛋白甲基化修飾對pleiotrophin信號通路的維持和多種肺癌細(xì)胞增殖所必需,。發(fā)現(xiàn)menin蛋白直接結(jié)合在基因組中PTN啟動子區(qū)域,，顯著提高該區(qū)域H3K27組蛋白三甲基化水平，但是并不影響該區(qū)域H3K4組蛋白甲基化修飾,，證實了通過MLLs影響基因組的H3K4甲基化修飾可能不是menin唯一的表觀遺傳調(diào)控特性,。同時，課題組還利用大量肺癌臨床標(biāo)本檢測證實了上述發(fā)現(xiàn),。
該研究成果將有助于闡明有關(guān)肺癌發(fā)生的嶄新的表觀遺傳學(xué)機(jī)制及其信號通路,，擴(kuò)展對menin介導(dǎo)的組蛋白修飾特點及規(guī)律等領(lǐng)域的認(rèn)識，對今后menin低表達(dá)肺癌的PTN/ALK為靶點的肺癌治療具有積極的指導(dǎo)意義,。（生物谷Bioon.com）
生物谷推薦原始出處：
Oncogene advance online publication 14 September 2009; doi: 10.1038/onc.2009.273
Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophin
S-B Gao1,4, Z-J Feng1,4, B Xu1, Y Wu1, P Yin2, Y Yang3, X Hua1,3 and G-H Jin1
1Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China
2Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
3Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA
Correspondence: Dr X Hua, Department of Cancer Biology, University of Pennsylvania, Room 412, BRBII/III, 421 Curie Blvd, Philadelphia, PA, 19096, USA.; Dr G-H Jin, Department of Basic Medical Sciences, Medical College, Xiamen University, Daxue road 168, Xiamen 361005, Fujian, PR China.
4These authors contributed equally to this work.
Menin upregulates transcription of cell-cycle inhibitors to suppress endocrine tumors, but it is poorly understood how menin suppresses non-endocrine tumors such as lung cancer. Here, we show that menin inhibits proliferation of human lung cancer cells and growth of lung cancer in mice. The menin-mediated tumor suppression requires repression of growth factor pleiotrophin (PTN), which binds to its cell surface receptor, anaplastic lymphoma kinase (ALK) that is activated in certain lung adenocarcinomas. Menin represses PTN transcription and PTN-induced proliferation of human lung cancer cells, and menin expression is substantially reduced in primary human lung adenocarcinomas. Notably, menin binds the PTN locus and enhances Polycomb gene Enhancer of Zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27m3), a negative mark for gene transcription but does not affect histone H3K4 methylation that is usually upregulated by menin in endocrine cells. Together, our findings indicate that menin suppresses lung cancer partly through increasing Polycomb gene-mediated H3K27 methylation and repressing PTN transcription, unraveling a novel, epigenetically regulated PTN–ALK signaling pathway in suppressing lung cancer.
