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

BMC Genomic Data - Tập 22 Số 1 - 2021
Emiel P. C. van der Vorst1, Mario Pepe2, Linsey J. F. Peters1, Markus Haberbosch1, Yvonne Jansen1, Ronald Naumann3, Georgios T. Stathopoulos2, Kiril Bidzhekov1
1Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität (LMU) München, Munich, Germany
2Helmholtz Center Munich, Munich, Germany.
3MPI of Molecular Cell Biology and Genetics, Dresden, Germany

Tóm tắt

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.

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