Identification of a potentially novel LncRNA-miRNA-mRNA competing endogenous RNA network in pulmonary arterial hypertension via integrated bioinformatic analysis

竞争性内源性RNA 小RNA 生物 计算生物学 核糖核酸 基因调控网络 信使核糖核酸 基因表达 基因 长非编码RNA 生物信息学 遗传学
作者
Jiantao Liu,Yupeng Sun,Bingqing Zhu,Yufan Lin,Kexin Lin,Yiruo Sun,Zhengze Yao,Lv‐Bing Yuan
出处
期刊:Life Sciences [Elsevier]
卷期号:277: 119455-119455 被引量:14
标识
DOI:10.1016/j.lfs.2021.119455
摘要

Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease with a cancer-like phenotype. Competing endogenous RNA (ceRNA) networks extensively involve in its pathological processes. But rare ceRNA networks and profound molecular mechanisms have been revealed in PAH. The aim of this study was to illuminate the ceRNA networks in PAH. In this work, we have chosen the idiopathic PAH as an example. GSE15197 (mRNA) and GSE56914 (miRNA) from the Gene Expression Omnibus (GEO) were selected to explore key genes and novel ceRNA networks in PAH by a series of integrated bioinformatic analysis. To be more scientific, a part of pairs in identified ceRNA network were detected in hypoxia-induced HPASMCs. And the dual-luciferase assay was performed to certify the relationship between miRNAs and mRNAs. Totally, 311 differentially expressed genes (DEGs) were identified and functional enrichment analysis illuminated that the majority of DEGs were enriched in proliferation, anti-apoptosis, inflammation and cancer-related pathways. And 10 hub genes were determined via Cytohubba after PPI network construction. Sequentially, with stepwise reverse prediction and pan-cancer co-expression analysis from mRNA to LncRNA in TargetScan, miRNet, ENCORI (Starbase V3.0) databases, a crucially ceRNA network was identified including 14 LncRNAs, 2 miRNAs, and 3 mRNAs. Further, in hypoxia-induced HPASMCs, the alterations of mRNAs, miRNAs and LncRNAs and their relationship were in accordance with the results we identified. Consequently, the unique hub genes and ceRNA network we proposed may advance our understanding of the molecular mechanisms in PAH.
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