Integrative Analyses of Whole-Transcriptome Sequencing Reveals CeRNA Regulatory Network of mRNAs, lncRNAs, miRNAs and circRNAs in Pulmonary Hypertension Treated with FGF21

Abstract

Abstract Noncoding RNAs have been shown to play important roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNA, miRNA, lncRNA, and circRNA were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Through intersection and predictive analysis, differentially co-expressed mRNA, miRNA, lncRNA, and circRNA were selected, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. A ceRNA regulatory network was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. Then the quantitative real time-PCR validation results were consistent with the results of whole-transcriptome sequencing. This study may provide potential biomarkers, pathway and ceRNA regulatory network in HPH treated with FGF21.