P14 New transcriptional alterations in the pathogenesis of type 2 diabetes, its potential regulation by micro RNAs

Authors

  • María Victoria Mencucci Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina
  • Ana María Rojas Mendoza Laboratory of Computational Biology and Bioinformatics (Andalusian Center for Developmental Biology), Spain
  • Eduardo Andés León Bioinformatics Unit (Institute of Parasitology and Biomedicine, López-Neyra, Spain
  • Carolina Román Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina
  • Luis Emilio Flores Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina
  • Juan José Gagliardino Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina
  • Martín Abba Center for Basic and Applied Immunological Research (CINIBA), Faculty of Medical Sciences, National University of La Plata, Province of Buenos Aires, Argentina
  • Bárbara Maiztegui Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina

DOI:

https://doi.org/10.47196/diab.v54i3Sup.395

Keywords:

transcriptional alterations, type 2 diabetes, micro RNAs

Abstract

Introduction: β cell dysfunction is conditioned by gene expression alterations and their regulatory mechanisms. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting and targeting messenger RNA (mRNAs). An adequate integration of mRNA and miRNA expression profiles facilitates elucidation of significant biological alterations.

Aim: to identify new transcriptomic alterations and miRNAs involved in type 2 diabetes (T2D) pathogenesis through the integration of data available in public databases.

Materials and methods: 1. 7 microarray studies performed from islets of people without diabetes (ND; n = 245) and with T2D (n = 96) were analyzed. For further meta-analysis, we identified Differentially Expressed Genes (DEGs) (ND vs. DT2) and selected those that varied consistently in the different studies. 2. mRNA and miRNA expression profiles were integrated, and computationally predicted miRNA-mRNA interactions to find dysregulated miRNAs relevant to T2D pathogenesis. This analysis was performed using a study from a T2D murine model in which both types of RNAs were analyzed in the same pancreatic tissue, using Next Generation Sequencing techniques.

Results: 1. As a result of meta-analysis, 48 transcriptional alterations associated with metabolism and/or development and maintenance of pancreatic islets were identified.
Notably, 9 of these DEGs have not been previously reported as dysregulated in T2D. 2. In the murine model, a total of 643 DEGs and 90 differentially expressed miRNAs (ND vs. DT2) were found. The integration analysis revealed 42 interactions involving 30 miRNAs and 33 mRNAs. Functional analyses indicated that lipid metabolism was enriched. In order to verify whether these interactions may be relevant in human, human
homologous miRNAs were searched, and their target genes were predicted. Six of these predicted interactions were also identified as relevant in the rat model, for example hsamir 29b-3p-COL5A3. In addition, 46 interactions involved mRNAs that are part of the transcriptional alterations found in point 1.

Conclusions: Our work provides new evidence that facilitates the interpretation of molecular alterations in T2D pathogenesis. Further studies could validate its potential use for the development of new strategies to improve T2D diagnosis and treatment.

Author Biography

Juan José Gagliardino, Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata (UNLP)-National Council for Scientific and Technical Research (CONICET), La Plata, Province of Buenos Aires, Argentina

Biochemist

Published

2023-01-10

How to Cite

Mencucci, M. V., Rojas Mendoza, A. M., León, E. A., Román, C., Flores, L. E., Gagliardino, J. J., Abba, M., & Maiztegui, B. (2023). P14 New transcriptional alterations in the pathogenesis of type 2 diabetes, its potential regulation by micro RNAs. Journal of the Argentine Society of Diabetes, 54(3Sup), 119–119. https://doi.org/10.47196/diab.v54i3Sup.395

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