Department of Geriatrics, Hypertension Department, Fujian Hypertension Research Institute, Clinical Research Center for Geriatric Hypertension Disease of Fujian Province, Branch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Department of General Practice, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
J Immunol Res. 2022 Sep 21;2022:7260801. doi: 10.1155/2022/7260801. eCollection 2022.
Myocardial ischemia/reperfusion (MI/R) injury is a common pathology in ischemia heart disease. Long noncoding RNAs (lncRNAs) are significant regulators related to many ischemia/reperfusion conditions. This study is aimed at exploring the molecule mechanism of lncRNA-mediated competing endogenous RNA (ceRNA) network in MI/R.
The dataset profiles of MI/R and normal tissues (GSE130217 and GSE124176) were obtained from the GEO database. Integrated bioinformatics were performed to screen out differentially expressed genes (DEGs). Thereafter, an lncRNA-mediated ceRNA network was constructed by the starBase database. The GO annotations and KEGG pathway analysis were conducted to study action mechanism and related pathways of DEGs in MI/R. A model of hypoxia/reoxygenation- (H/R-) treated HL-1 cell was performed to verify the expression of lncRNAs through qRT-PCR.
2406 differentially expressed- (DE-) mRNAs, 70 DE-lncRNAs, and 156 DE-miRNAs were acquired. These DEGs were conducted to construct an lncRNA-mediated ceRNA network, and a subnetwork including lncRNA Xist/miRNA-133c/mRNA (Slc30a9) was screen out. The functional enrichment analyses revealed that the lncRNAs involved in the ceRNA network might functions in oxidative stress and calcium signaling pathway. The lncRNA Xist expression is reduced under H/R conditions, followed by the increased level of miRNA-133c, thus downregulating the expression of Slc30a9.
In sum, the identified ceRNA network which included the lncRNA Xist/miR-133c/Slc30a9 axis might contribute a better understanding to the pathogenesis and development of MI/R injury and offer a novel targeted therapy way.
心肌缺血/再灌注（MI/R）损伤是缺血性心脏病的一种常见病理。长链非编码 RNA（lncRNA）是与许多缺血/再灌注情况相关的重要调节因子。本研究旨在探讨 lncRNA 介导的竞争内源性 RNA（ceRNA）网络在 MI/R 中的分子机制。
从 GEO 数据库中获取 MI/R 和正常组织的数据集谱（GSE130217 和 GSE124176）。通过整合生物信息学筛选出差异表达基因（DEGs）。然后，通过 starBase 数据库构建 lncRNA 介导的 ceRNA 网络。通过 GO 注释和 KEGG 通路分析研究 MI/R 中 DEGs 的作用机制和相关通路。通过 qRT-PCR 验证 HL-1 细胞缺氧/复氧（H/R）处理后的 lncRNA 表达。
获得 2406 个差异表达-（DE-）mRNA、70 个 DE-lncRNA 和 156 个 DE-miRNA。这些 DEGs 用于构建 lncRNA 介导的 ceRNA 网络，并筛选出包括 lncRNA Xist/miRNA-133c/mRNA（Slc30a9）在内的子网络。功能富集分析表明，ceRNA 网络中涉及的 lncRNA 可能在氧化应激和钙信号通路中发挥作用。在 H/R 条件下，lncRNA Xist 的表达降低，随后 miRNA-133c 的水平升高，从而下调 Slc30a9 的表达。
总之，确定的 ceRNA 网络，包括 lncRNA Xist/miR-133c/Slc30a9 轴，可能有助于更好地理解 MI/R 损伤的发病机制和发展，并提供新的靶向治疗方法。
