Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model

• Published in: Genomics (San Diego, Calif.) Vol. 113; no. 1; pp. 11 - 19
• Main Authors: Xu, Shuang-Lan, Deng, Yi-Shu, Liu, Jie, Xu, Shuang-Yan, Zhao, Fang-Yun, Wei, Li, Tian, Ying-Chun, Yu, Cai-E, Cao, Bing, Huang, Xiao-Xian, Yang, Mei, He, Xiao-Hua, Bai, Min, Huang, Yun-Chao, Xing, Xi-Qian, Yang, Jiao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2021
• Subjects: Animals; Bioinformatics analysis; Circular RNA; Competitive endogenous RNA; Gene Regulatory Networks; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - metabolism; Hypoxia - genetics; Hypoxia - metabolism; Hypoxic pulmonary hypertension; Male; MAP Kinase Signaling System; microRNA; NF-kappa B - metabolism; Protein Interaction Maps; Rats; Rats, Sprague-Dawley; RNA, Circular - genetics; RNA, Circular - metabolism; RNA-Seq; Toll-Like Receptors - metabolism; Transcriptome; Bioinformatics analysis; Circular RNA; microRNA; Hypoxic pulmonary hypertension; RNA-Seq; Competitive endogenous RNA
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2020.11.021

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.
•The HPH rat model was successfully constructed.•Dysregulated circRNAs/miRNAs/mRNAs of HPH from rat lung tissues were integrated, and a circRNA-miRNA-mRNA ceRNA regulatory network was constructed.•A variety of novel genes (including circRNAs/miRNAs/mRNAs) and pathways (including KEGG pathway and ceRNA network) were possibly involved in the occurrence and development of HPH.•The qRT-PCR validation results were consistent with the RNA-Seq results.