4.7 Article

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

Journal

GENOMICS
Volume 113, Issue 1, Pages 11-19

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2020.11.021

Keywords

Hypoxic pulmonary hypertension; Circular RNA; microRNA; Competitive endogenous RNA; RNA-Seq; Bioinformatics analysis

Funding

  1. National Natural Science Foundation of China [81560694, 81760015]
  2. Yunnan Provincial Science and Technology Department and Kunming Medical University [2018FE001(206), 2017FE467(094)]
  3. Yunnan Health Training Project of High Level Talents [D-201627, H-2018095]
  4. Famous Doctors of Highlevel Talent Training Support Program of Yunnan Province
  5. Young Academic and Technical Leaders of Yunnan Province [2017HB053]

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This study identified potential critical genes and circRNAs acting as ceRNAs in a HPH rat model. A ceRNA network was constructed, showing association with inflammatory response, NF-kappa B signaling, MAPK cascade, and Toll-like receptor. Certain circRNAs could potentially control downstream target genes by sponging miR-23a or miR-21 in the pathophysiology of HPH, as confirmed by qRT-PCR validation.
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-kappa B 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.

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