Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-08-31 DOI:10.1007/s13258-024-01547-1
Du Hyeong Lee, Eun Gyung Park, Jung-Min Kim, Hae Jin Shin, Yun Ju Lee, Hyeon-Su Jeong, Hyun-Young Roh, Woo Ryung Kim, Hongseok Ha, Sang-Woo Kim, Yung Hyun Choi, Heui-Soo Kim
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Abstract

Background: Transposable elements (TEs) are known to be inserted into genome to create transcript isoforms or to generate long non-coding RNA (lncRNA) sequences. The insertion of TEs generates a gene protein sequence within the genome, but also provides a microRNA (miRNA) regulatory region.

Objective: To determine the effect of gene sequence changes caused by TE insertion on miRNA binding and to investigate the formation of an overlapping lncRNA that represses it.

Methods: The distribution of overlapping regions between exons and TE regions with lncRNA was examined using the Bedtools. miRNAs that can bind to those overlapping regions were identified through the miRDB web program. For TE-lncRNA overlapping genes, bioinformatic analysis was conducted using DAVID web database. Differential expression analysis was conducted using data from the GEO dataset and TCGA.

Results: Most TEs were distributed more frequently in untranslated regions than open reading frames. There were 30 annotated TE-lncRNA overlapping genes with same strand that could bind to the same miRNA. As a result of identifying the association between these 30 genes and diseases, TGFB2, FCGR2A, DCTN5, and IFI6 were associated with breast cancer, and HMGCS1, FRMD4A, EDNRB, and SNCA were associated with Alzheimer's disease. Analysis of the GEO and TCGA data showed that the relevant expression of miR-891a and miR-28, which bind to the TE overlapping region of DCTN5 and HMGCS1, decreased.

Conclusion: This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.

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TE-lncRNA 重叠基因与 miRNA 在人类疾病中错综复杂的相互作用的基因组分析。
背景:已知可转座元件(TE)可插入基因组以产生转录本异构体或长非编码RNA(lncRNA)序列。可逆元件的插入会在基因组中产生基因蛋白序列,同时也会提供微RNA(miRNA)调控区域:确定TE插入引起的基因序列变化对miRNA结合的影响,并研究抑制miRNA的重叠lncRNA的形成:方法:利用Bedtools检测外显子和TE区域与lncRNA重叠区域的分布。对于TE-lncRNA重叠基因,使用DAVID网络数据库进行了生物信息学分析。利用GEO数据集和TCGA的数据进行了差异表达分析:结果:与开放阅读框相比,大多数TE更频繁地分布在非翻译区。有30个注释的TE-lncRNA重叠基因具有相同的链,可与相同的miRNA结合。通过分析这30个基因与疾病的关系,发现TGFB2、FCGR2A、DCTN5和IFI6与乳腺癌有关,HMGCS1、FRMD4A、EDNRB和SNCA与阿尔茨海默病有关。对 GEO 和 TCGA 数据的分析表明,与 DCTN5 和 HMGCS1 的 TE 重叠区结合的 miR-891a 和 miR-28 的相关表达量下降:本研究表明,TE-lncRNA重叠基因与miRNA之间的相互作用会影响疾病的进展。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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