Department of Cardiology, The Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang, 050000, Hebei, China.
BMC Med Genomics. 2023 Mar 9;16(1):51. doi: 10.1186/s12920-023-01478-y.
Stroke attributable to atrial fibrillation (AF related stroke, AFST) accounts for 13 ~ 26% of ischemic stroke. It has been found that AFST patients have a higher risk of disability and mortality than those without AF. Additionally, it's still a great challenge to treat AFST patients because its exact mechanism at the molecular level remains unclear. Thus, it's vital to investigate the mechanism of AFST and search for molecular targets of treatment. Long non-coding RNAs (lncRNAs) are related to the pathogenesis of various diseases. However, the role of lncRNAs in AFST remains unclear. In this study, AFST-related lncRNAs are explored using competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA).
GSE66724 and GSE58294 datasets were downloaded from GEO database. After data preprocessing and probe reannotation, differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) between AFST and AF samples were explored. Then, functional enrichment analysis and protein-protein interaction (PPI) network analysis of the DEMs were performed. At the meantime, ceRNA network analysis and WGCNA were performed to identify hub lncRNAs. The hub lncRNAs identified both by ceRNA network analysis and WGCNA were further validated by Comparative Toxicogenomics Database (CTD).
In all, 19 DELs and 317 DEMs were identified between the AFST and AF samples. Functional enrichment analysis suggested that the DEMs associated with AFST were mainly enriched in the activation of the immune response. Two lncRNAs which overlapped between the three lncRNAs identified by the ceRNA network analysis and the 28 lncRNAs identified by the WGCNA were screened as hub lncRNAs for further validation. Finally, lncRNA GAS6-AS1 turned out to be associated with AFST by CTD validation.
These findings suggested that low expression of GAS6-AS1 might exert an essential role in AFST through downregulating its downstream target mRNAs GOLGA8A and BACH2, and GAS6-AS1 might be a potential target for AFST therapy.
由心房颤动（房颤相关卒中，AFST）引起的中风占缺血性中风的 13%~26%。已经发现，AFST 患者的残疾和死亡风险高于没有房颤的患者。此外，由于其在分子水平的确切机制尚不清楚，因此治疗 AFST 患者仍然是一个巨大的挑战。因此，研究 AFST 的发病机制并寻找治疗的分子靶点至关重要。长链非编码 RNA（lncRNA）与各种疾病的发病机制有关。然而，lncRNA 在 AFST 中的作用尚不清楚。在这项研究中，使用竞争性内源 RNA（ceRNA）网络分析和加权基因共表达网络分析（WGCNA）来探索 AFST 相关的 lncRNA。
从 GEO 数据库下载 GSE66724 和 GSE58294 数据集。在数据预处理和探针重新注释后，探索 AFST 和 AF 样本之间差异表达的 lncRNA（DEL）和差异表达的 mRNA（DEM）。然后，对 DEMs 进行功能富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。同时，进行 ceRNA 网络分析和 WGCNA 以鉴定 hub lncRNA。ceRNA 网络分析和 WGCNA 均鉴定出的 hub lncRNA 通过比较毒理学基因组数据库（CTD）进一步验证。
共鉴定出 19 个 DEL 和 317 个 DEM 在 AFST 和 AF 样本之间存在差异。功能富集分析表明，与 AFST 相关的 DEMs 主要富集在免疫反应的激活中。ceRNA 网络分析鉴定的三个 lncRNA 中重叠的两个 lncRNA 和 WGCNA 鉴定的 28 个 lncRNA 被筛选为进一步验证的 hub lncRNA。最后，通过 CTD 验证发现 lncRNA GAS6-AS1 与 AFST 相关。
这些发现表明，GAS6-AS1 的低表达可能通过下调其下游靶基因 GOLGA8A 和 BACH2 在 AFST 中发挥重要作用，GAS6-AS1 可能是 AFST 治疗的潜在靶点。
