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卫星重复序列HSAT5和转座元件的表达与胶质瘤的疾病进展和生存期有关。

Expressions of the satellite repeat HSAT5 and transposable elements are implicated in disease progression and survival in glioma.

作者信息

Köse Sıla Naz, Yaraş Tutku, Bursali Ahmet, Oktay Yavuz, Yandim Cihangir, Karakülah Gökhan

机构信息

Department of Genetics and Bioengineering, Faculty of Engineering, İzmir University of Economics, İzmir, Turkiye.

İzmir Biomedicine and Genome Center (IBG), İzmir, Turkiye.

出版信息

Turk J Biol. 2024 Jul 1;48(4):242-256. doi: 10.55730/1300-0152.2700. eCollection 2024.

Abstract

The glioma genome encompasses a complex array of dysregulatory events, presenting a formidable challenge in managing this devastating disease. Despite the widespread distribution of repeat and transposable elements across the human genome, their involvement in glioma's molecular pathology and patient survival remains largely unexplored. In this study, we aimed to characterize the links between the expressions of repeat/transposable elements with disease progression and survival in glioma patients. Hence, we analyzed the expression levels of satellite repeats and transposons along with genes in low-grade glioma (LGG) and high-grade glioma (HGG). Endogenous transposable elements LTR5 and HERV_a-int exhibited higher expression in HGG patients, along with immune response-related genes. Altogether, 16 transposable elements were associated with slower progression of disease in LGG patients. Conversely, 22 transposons and the HSAT5 satellite repeat were linked to a shorter event-free survival in HGG patients. Intriguingly, our weighted gene coexpression network analysis (WGCNA) disclosed that the HSAT5 satellite repeat resided in the same module network with genes implicated in chromosome segregation and nuclear division; potentially hinting at its contribution to disease pathogenesis. Collectively, we report for the first time that repeat and/or transposon expression could be related to disease progression and survival in glioma. The expressions of these elements seem to exert a protective effect during LGG-to-HGG progression, whereas they could have a detrimental impact once HGG is established. The results presented herein could serve as a foundation for further experimental work aimed at elucidating the molecular regulation of glioma genome.

摘要

胶质瘤基因组包含一系列复杂的失调事件,这给管理这种毁灭性疾病带来了巨大挑战。尽管重复元件和转座元件广泛分布于人类基因组中,但它们在胶质瘤分子病理学和患者生存中的作用在很大程度上仍未得到探索。在本研究中,我们旨在明确重复元件/转座元件的表达与胶质瘤患者疾病进展和生存之间的联系。因此,我们分析了低级别胶质瘤(LGG)和高级别胶质瘤(HGG)中卫星重复序列、转座子以及基因的表达水平。内源性转座元件LTR5和HERV_a-int在HGG患者中与免疫反应相关基因一起呈现出更高的表达。总共,16个转座元件与LGG患者疾病进展较慢相关。相反,22个转座子和HSAT5卫星重复序列与HGG患者较短的无事件生存期相关。有趣的是,我们的加权基因共表达网络分析(WGCNA)表明,HSAT5卫星重复序列与参与染色体分离和核分裂的基因位于同一个模块网络中;这可能暗示了它对疾病发病机制的作用。总体而言,我们首次报道重复元件和/或转座子表达可能与胶质瘤的疾病进展和生存相关。这些元件的表达在LGG向HGG进展过程中似乎发挥了保护作用,而一旦HGG形成,它们可能会产生有害影响。本文呈现的结果可为进一步阐明胶质瘤基因组分子调控的实验工作奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e9/11407350/67a6c9e11ae0/tjb-48-04-242f1.jpg

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