ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta

Int J Mol Sci. 2021 Mar 28;22(7):3497. doi: 10.3390/ijms22073497.

Abstract

The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to vertebrates, is an excellent model to investigate mechanisms of post-transcriptional regulation evolutionarily highly conserved in immune homeostasis. The combined use of NGS and bioinformatic analyses suggests that in the pharynx, the hematopoietic organ of Ciona robusta, the Tgf-β, Wnt, Hedgehog and FoxO pathways are involved in tissue homeostasis, as they are in human. Furthermore, ceRNA network interactions and 3'UTR elements analyses of Tgf-β, Wnt, Hedgehog and FoxO pathways genes suggest that different miRNAs conserved (cin-let-7d, cin-mir-92c, cin-mir-153), species-specific (cin-mir-4187, cin-mir-4011a, cin-mir-4056, cin-mir-4150, cin-mir-4189, cin-mir-4053, cin-mir-4016, cin-mir-4075), pseudogenes (ENSCING00000011392, ENSCING00000018651, ENSCING00000007698) and mRNA 3'UTR elements are involved in post-transcriptional regulation in an integrated way in C. robusta.

Keywords: FOXO; NGS; TGF-β; WNT; ascidian; miRNA; pseudogenes.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Lineage
  • Ciona / metabolism*
  • Computational Biology
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation*
  • Hedgehog Proteins / metabolism
  • Hematopoiesis
  • High-Throughput Nucleotide Sequencing
  • Homeostasis
  • Immune System
  • MicroRNAs / metabolism
  • Pharynx / metabolism
  • Protein Interaction Mapping
  • RNA-Seq
  • Transforming Growth Factor beta / metabolism*
  • Wnt Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Forkhead Box Protein O1
  • Hedgehog Proteins
  • MicroRNAs
  • Transforming Growth Factor beta
  • Wnt Proteins