对人类疾病中 TE-lncRNA 重叠基因与 miRNA 的复杂相互作用进行基因组分析。
Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.
发表日期:2024 Aug 31
作者:
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
来源:
Alzheimers & Dementia
摘要:
已知转座元件 (TE) 可以插入基因组中以创建转录异构体或生成长非编码 RNA (lncRNA) 序列。 TE 的插入在基因组内生成基因蛋白序列,同时还提供了 microRNA (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 结合的重叠 lncRNA 的形成使用 Bedtools 检查外显子和 TE 区域与 lncRNA 之间重叠区域的分布。通过 miRDB 网络程序鉴定了可以与这些重叠区域结合的 miRNA。对于TE-lncRNA重叠基因,使用DAVID网络数据库进行生物信息学分析。使用来自 GEO 数据集和 TCGA 的数据进行差异表达分析。大多数 TE 比开放阅读框更频繁地分布在非翻译区域。有30个注释的TE-lncRNA重叠基因具有相同的链,可以结合相同的miRNA。确定这 30 个基因与疾病之间的关联的结果是,TGFB2、FCGR2A、DCTN5 和 IFI6 与乳腺癌相关,HMGCS1、FRMD4A、EDNRB 和 SNCA 与阿尔茨海默病相关。 GEO和TCGA数据分析显示,与DCTN5和HMGCS1的TE重叠区域结合的miR-891a和miR-28的相关表达下降。本研究表明TE-lncRNA重叠基因与miRNA之间的相互作用可以影响疾病进展。© 2024。作者获得韩国遗传学会的独家许可。
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.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.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.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.This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.