Aberrant nuclear lamina contributes to the malignancy of human gliomas  

作　　者：Shunqi Pei Xuehui Wang Xuan Wang Hao Huang Huaping Tao Binghua Xie Aifen Yang Mengsheng Qiu Zhou Tan 

机构地区：[1]Institute of Life Sciences,Key Laboratory of Organ Development and Regeneration of Zhejiang Province,College of Life Sciences,Hangzhou Normal University,Zhejiang 311121,China

出　　处：《Journal of Genetics and Genomics》2022年第2期132-144,共13页遗传学报（英文版）

基　　金：supported by grants from High-level students returning to China (team) project in Hangzhou (2017);Zhejiang Provincial Natural Science Foundation of China (LY19C090002, LQ18C090005);Hangzhou Agriculture and Social Development Project (20191203B20)。

摘　　要：Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.

关 键 词：GLIOMAS Proteomics GENOMICS Nucleus LAMINS MALIGNANCY 

分 类 号：R739.41[医药卫生—肿瘤]