Transcriptome signature of miRNA-26b KO mouse model suggests novel targets

Emiel P. C. van der Vorst*, Mario A. A. Pepe, Linsey J. F. Peters, Markus Haberbosch, Yvonne Jansen, Ronald Nauman, Georgios T. Stathopoulos, Christian Weber, Kiril Bidzhekov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

Abstract

Background MicroRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. Results A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. Conclusions miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies.

Original languageEnglish
Article number23
Number of pages14
JournalBMC Genomic Data
Volume22
Issue number1
DOIs
Publication statusPublished - 30 Jun 2021

Keywords

  • MicroRNA-26b
  • Knock-out mouse model
  • Next generation sequencing
  • Cancer
  • Neurological disorders
  • Cardiovascular disease
  • Thermogenesis
  • Allergic reactions
  • MICRORNA EXPRESSION
  • WNK KINASES
  • SURVIVAL
  • DECTIN-2
  • GROWTH

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