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

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2024-07-01 eCollection Date: 2024-01-01 DOI:10.55730/1300-0152.2700
Sıla Naz Köse, Tutku Yaraş, Ahmet Bursali, Yavuz Oktay, Cihangir Yandim, Gökhan Karakülah
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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.

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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存活率有关。
胶质瘤基因组包含一系列复杂的失调事件,给治疗这种毁灭性疾病带来了巨大挑战。尽管重复和转座元件在人类基因组中广泛分布,但它们与胶质瘤的分子病理学和患者生存之间的关系在很大程度上仍未得到探讨。在这项研究中,我们旨在分析重复/可转座元件的表达与胶质瘤患者的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)中卫星重复序列和转座子以及基因的表达水平。内源性转座元件LTR5和HERV_a-int以及免疫反应相关基因在HGG患者中的表达量较高。在 LGG 患者中,共有 16 个转座子与疾病进展缓慢有关。相反,22 个转座子和 HSAT5 卫星重复与 HGG 患者较短的无事件生存期有关。耐人寻味的是,我们的加权基因共表达网络分析(WGCNA)发现,HSAT5 卫星重复序列与染色体分离和核分裂相关基因位于同一模块网络中;这可能暗示了它对疾病发病机制的贡献。总之,我们首次报告了重复和/或转座子的表达可能与胶质瘤的疾病进展和存活有关。在 LGG 向 HGG 演变的过程中,这些元素的表达似乎具有保护作用,而一旦 HGG 确立,它们可能会产生有害影响。本文介绍的结果可为进一步开展旨在阐明胶质瘤基因组分子调控的实验工作奠定基础。
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