Abnormal expression of menin predicts the pathogenesis and poor prognosis of adult gliomas
Abnormal expression of menin predicts the pathogenesis and poor prognosis of adult gliomas
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menin的异常表达预示着成人胶质瘤的发病机制和不良预后
DOI：
10.1038/s41417-019-0127-5
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发表时间：
--
影响因子：
6.4
通讯作者：
Guang-Hui Jin
中科院分区：
文献类型：
--
作者：
Zhan-Feng Wang;Xin-Yu Hong;Ling-Yu Zhu;Li Zhang;Huan Qiu;Yuan-Yuan Zhang;Ming-Cheng Yuan;Xing-Li Zhao;Qi-Fan Zheng;Guang-Hui Jin
许多脑肿瘤的发生与染色质组蛋白修饰异常密切相关，而高度恶性的成人胶质瘤发生的表观遗传学机制尚未得到深入研究。MEN 1基因编码表观遗传调节因子menin，其缺失或突变可特异性诱导低分化神经内分泌肿瘤;然而，MEN 1在神经系统中的生物学和临床重要性仍知之甚少。44.4%的成年胶质瘤中Menin表达被强烈激活。menin的异常高表达与中位生存期（20个月）较短、肿瘤体积较大和Ki 67染色百分比较高密切相关。有趣的是，menin在肿瘤细胞的胞浆中也有表达（38.8%），并且也与胶质瘤患者的不良预后密切相关。重要的是，在对96种小分子靶向组蛋白修饰调节剂的筛选中，发现menin抑制剂可显著阻断成人胶质瘤细胞的增殖。我们的研究结果证实，menin是一个潜在的生物标志物，预后不良的成人胶质瘤，独立的WHO分级。以menin为靶点可以有效抑制某些胶质瘤，这一信息为胶质瘤的治疗策略提供了新的见解。
Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of theMEN1gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance ofMEN1in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.