Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China.
National Health Commission Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, Hunan, PR China; Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, PR China; Hunan Provincial Key Laboratory of Neurorestoratology, Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan, PR China.
Life Sci. 2021 Jan 15;265:118861. doi: 10.1016/j.lfs.2020.118861. Epub 2020 Dec 7.
AIMS: LncRNAs are involved in many biological processes, and hypoxia contributed to the alterations of lncRNAs. Hypoxic preconditioned olfactory mucosa mesenchymal stem cells (OM-MSCs) exerted stronger anti-apoptotic ability in models of disease, but the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions were unclear. The present study was aimed to explore the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions. MAIN METHODS: LncRNAs and mRNAs expression profiles of human OM-MSCs between hypoxic (3%) and normoxic conditions were analyzed by Next-Generation Sequencing (NGS) analysis, bioinformatics analysis on these data were further performed. Moreover, loss-of function assay was conducted to investigate the impact of hypoxic condition on the proliferation and apoptosis of OM-MSCs. KEY FINDINGS: Through the comparative analysis and bioinformatics analysis, a total of 1741 lncRNAs and 1603 mRNAs were significant differentially expressed in the hypoxia group compared with normoxia group. Enrichment analysis revealed that differentially expressed genes of human OM-MSCs mainly participated in cell cycle regulation, secretin of cytokines and so on. Meanwhile, hypoxic condition significantly promoted proliferation and inhibited apoptosis of human OM-MSCs, following loss-of-function assays confirmed that lncRNA DARS-AS1 were involved in this regulatory process by hypoxic condition. Further prediction of targeted genes and the construction of lncRNA-miRNA-mRNA interaction network enriched the significance regarding the mechanism of DARS-AS1. SIGNIFICANCE: Altogether, these findings provided a new perspective for understanding the molecules expression patterns in hypoxia that contributed to corresponding phenotype alterations of OM-MSCs.
目的:长链非编码 RNA(lncRNAs)参与许多生物学过程,而缺氧会导致 lncRNAs 的改变。缺氧预处理的嗅黏膜间充质干细胞(OM-MSCs)在疾病模型中表现出更强的抗凋亡能力,但控制 OM-MSCs 在缺氧和常氧条件下不同生物学特性的分子尚不清楚。本研究旨在探讨控制 OM-MSCs 在缺氧和常氧条件下不同生物学特性的分子。
主要方法:通过下一代测序(NGS)分析分析 OM-MSCs 在缺氧(3%)和常氧条件下的 lncRNAs 和 mRNAs 表达谱,进一步对这些数据进行生物信息学分析。此外,还进行了功能丧失实验,以研究缺氧条件对 OM-MSCs 增殖和凋亡的影响。
主要发现:通过比较分析和生物信息学分析,在缺氧组与常氧组相比,共鉴定出 1741 个 lncRNAs 和 1603 个 mRNAs 显著差异表达。富集分析表明,OM-MSCs 差异表达基因主要参与细胞周期调控、细胞因子分泌等过程。同时,缺氧条件显著促进 OM-MSCs 的增殖并抑制其凋亡,通过功能丧失实验进一步证实,lncRNA DARS-AS1 参与了这一调节过程。对靶向基因的进一步预测和 lncRNA-miRNA-mRNA 相互作用网络的构建丰富了 DARS-AS1 机制的意义。
意义:综上所述,这些发现为理解缺氧条件下 OM-MSCs 相应表型改变所涉及的分子表达模式提供了新的视角。