来自厦门大学医学院基础医学部的研究人员在肿瘤学研究权威杂志《癌基因》（Oncogene）上发表研究论文“Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophin” 。
文章的通讯作者是金光辉副教授和华先欣讲座教授，其实验室主要研究方向为抑癌基因转录调控与疾病发生关系，尤其在新发现的抑癌基因Men1及其编码蛋白menin的生物学功能方面进行了系统、深入的研究。
有关基因表达沉默的表观遗传调控体系的建立和维持是决定细胞表型、分化和功能特化的重要分子基础。以往的研究表明，抑癌基因MEN1及其编码蛋白menin通过与MLLs等组蛋白甲基化修饰酶相互作用而调节H3K4等正性组蛋白甲基化修饰，但是menin是否参与其他组蛋白修饰尚不清楚。课题组通过深入研究，首次证明了menin与Polycomb家族共同介导的H3K27组蛋白甲基化修饰对pleiotrophin信号通路的维持和多种肺癌细胞增殖所必需。发现menin蛋白直接结合在基因组中PTN启动子区域，显著提高该区域H3K27组蛋白三甲基化水平，但是并不影响该区域H3K4组蛋白甲基化修饰，证实了通过MLLs影响基因组的H3K4甲基化修饰可能不是menin唯一的表观遗传调控特性。同时，课题组还利用大量肺癌临床标本检测证实了上述发现。
该研究成果将有助于阐明有关肺癌发生的崭新的表观遗传学机制及其信号通路，扩展对menin介导的组蛋白修饰特点及规律等领域的认识，对今后menin低表达肺癌的PTN/ALK为靶点的肺癌治疗具有积极的指导意义。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
