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
• 来源期刊: 遗传学报
• 年，卷（期）: 2022,（2）
• 所属期刊栏目: Original Research
• 页码范围: 132-144
• 页数: 13页
• 语种: 英文

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 pro-gression in both in vitro and in vivo mouse models.Moreover,the repression of glioma cell growth by lamin knockdown is mediated by the pRb-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.