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Aberrant nuclear lamina contributes to the malignancy of human gliomas
Institution:1. Institute of Life Sciences, College of Life and Environmental Sciences, Key Laboratory of Mammalian Organogenesis and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China;2. The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China;1. Fujian Key Laboratory of Developmental and Neural Biology and Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350117, China;2. Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
Abstract: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 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.
Keywords:Gliomas  Proteomics  Genomics  Nucleus  Lamins  Malignancy
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