lncRNA-miRNA-mRNA ceRNA Network Involved in Sheep Prolificacy: An Integrated Approach

Genes (Basel). 2022 Jul 22;13(8):1295. doi: 10.3390/genes13081295.


Understanding the molecular pattern of fertility is considered as an important step in breeding of different species, and despite the high importance of the fertility, little success has been achieved in dissecting the interactome basis of sheep fertility. However, the complex mechanisms associated with prolificacy in sheep have not been fully understood. Therefore, this study aimed to use competitive endogenous RNA (ceRNA) networks to evaluate this trait to better understand the molecular mechanisms responsible for fertility. A competitive endogenous RNA (ceRNA) network of the corpus luteum was constructed between Romanov and Baluchi sheep breeds with either good or poor genetic merit for prolificacy using whole-transcriptome analysis. First, the main list of lncRNAs, miRNAs, and mRNA related to the corpus luteum that alter with the breed were extracted, then miRNA−mRNA and lncRNA−mRNA interactions were predicted, and the ceRNA network was constructed by integrating these interactions with the other gene regulatory networks and the protein−protein interaction (PPI). A total of 264 mRNAs, 14 lncRNAs, and 34 miRNAs were identified by combining the GO and KEGG enrichment analyses. In total, 44, 7, 7, and 6 mRNAs, lncRNAs, miRNAs, and crucial modules, respectively, were disclosed through clustering for the corpus luteum ceRNA network. All these RNAs involved in biological processes, namely proteolysis, actin cytoskeleton organization, immune system process, cell adhesion, cell differentiation, and lipid metabolic process, have an overexpression pattern (Padj < 0.01). This study increases our understanding of the contribution of different breed transcriptomes to phenotypic fertility differences and constructed a ceRNA network in sheep (Ovis aries) to provide insights into further research on the molecular mechanism and identify new biomarkers for genetic improvement.

Keywords: RNA-seq; corpus luteum; lncRNA–miRNA–mRNA ceRNA network; prolificacy; protein–protein interaction; sheep.

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sheep / genetics


  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger

Grants and funding

This research received no external funding.