Department of Emergency, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Cardiology, Hebei General Hospital, Shijiazhuang, China.
Mol Genet Genomic Med. 2021 Jan;9(1):e1557. doi: 10.1002/mgg3.1557. Epub 2020 Nov 25.
This study set out to determine key lncRNAs correlated with sepsis via constructing competing endogenous RNA (ceRNA) network.
Three septic patients and three healthy controls were recruited to obtain lncRNA profiles in this current study. Combined with the mRNA profiles by RNA-sequencing, an integrated analysis of mRNA expression profiles downloaded from GEO was performed to obtain the differentially expressed mRNAs (DEmRNAs). Based on differentially expressed lncRNAs (DElncRNAs) and DEmRNAs acquired in this present study and differentially expressed miRNAs (DEmiRNAs) acquired in previous study, a ceRNA network was constructed. Furthermore, LINC00963 was validated in THP-1 cells by performing loss of function assays.
In this analysis, a total of 290 DEmRNAs and 46 DElncRNAs were detected in sepsis. Parkinson's disease, Oxidative phosphorylation and Cardiac muscle contraction were significantly enriched KEGG pathways in sepsis. XPO1, CUL4A, and NEDD8 were three hub proteins of sepsis-specific PPI network. A ceRNA network, which contained 16 DElncRNA-DEmiRNA pairs and 82 DEmiRNA-DEmRNA pairs, involving 5 lncRNAs, 10 miRNAs, and 60 mRNAs, was obtained. The function experiments indicated that knockdown of LINC00963 could promote cell proliferation, reduce cytokine expression, and suppress inflammasome activation and phagocytosis in LPS-induced THP-1 cells.
This study determined key lncRNAs involved in sepsis, which may contribute to the development for novel treatment strategy of sepsis.
本研究旨在通过构建竞争性内源 RNA (ceRNA) 网络，确定与脓毒症相关的关键长链非编码 RNA (lncRNA)。
本研究招募了 3 名脓毒症患者和 3 名健康对照者，以获得 lncRNA 谱。结合 RNA-seq 获得的 mRNA 谱，对从 GEO 下载的 mRNA 表达谱进行综合分析，以获得差异表达的 mRNAs (DEmRNAs)。基于本研究中获得的差异表达 lncRNA (DElncRNAs) 和 DEmRNAs 以及先前研究中获得的差异表达 miRNAs (DEmiRNAs)，构建了 ceRNA 网络。此外，通过进行功能丧失实验，在 THP-1 细胞中验证了 LINC00963。
在这项分析中，在脓毒症中检测到 290 个 DEmRNAs 和 46 个 DElncRNAs。帕金森病、氧化磷酸化和心肌收缩是脓毒症中显著富集的 KEGG 通路。XPO1、CUL4A 和 NEDD8 是脓毒症特异性 PPI 网络的三个枢纽蛋白。获得了包含 16 个 DElncRNA-DEmiRNA 对和 82 个 DEmiRNA-DEmRNA 对的 ceRNA 网络，涉及 5 个 lncRNA、10 个 miRNA 和 60 个 mRNA。功能实验表明，LINC00963 的敲低可促进 LPS 诱导的 THP-1 细胞增殖，减少细胞因子表达，并抑制炎症小体激活和吞噬作用。
本研究确定了参与脓毒症的关键 lncRNA，这可能有助于开发脓毒症的新治疗策略。
