表达与LINE-1反义启动子活性相关的基因的泛癌症特征。

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Mobile DNA Pub Date : 2023-09-18 DOI:10.1186/s13100-023-00300-x
Baohong Xu, Xueer Li, Shaoqi Zhang, Meina Lian, Wenbin Huang, Yin Zhang, Yudong Wang, Zhiquan Huang
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引用次数: 0

摘要

背景:长散布核元件-1(LINE-1或L1)占人类基因组的17%。L1作为唯一自主和活性的反转录转座子,可能以某些方式参与癌症的发生和发展。L1在癌症中的研究主要集中在L1插入新基因组基因座的影响上。L1 5´非翻译区(UTR)也含有反义启动子(ASP)活性,产生与相邻外显子的L1基因嵌合转录物。据报道,这些ASP相关基因中的一些在癌症中过表达,并促进癌症细胞生长。然而,人们对L1-ASP相关基因在人类癌症中的总体表达模式和作用知之甚少。结果:L1-ASP相关基因在癌症中经常失调,并与细胞周期、PI3K/AKT通路和GTPase信号通路有关。L1 ASP相关基因的表达与肿瘤患者的预后相关。Hub L1 ASP相关基因CENPU和MCM2与全癌患者的免疫浸润、临床T分期和癌症干性相关。L1 ASP相关基因LINC00491的敲除导致肿瘤生长和迁移能力的显著降低。结论:L1 ASP相关基因的表达在全癌水平上显著失调,这与肿瘤微环境、进展和患者预后密切相关。中枢基因CENPU和MCM2有望成为新的肿瘤诊断标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity.

Background: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers.

Results: L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability.

Conclusions: The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.

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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
期刊最新文献
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