Integrated analysis of microRNA regulation and its interaction with mechanisms of epigenetic regulation in the etiology of systemic lupus erythematosus

PLoS One. 2019 Jun 25;14(6):e0218116. doi: 10.1371/journal.pone.0218116. eCollection 2019.

Abstract

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Epigenesis, Genetic*
  • Gene Ontology
  • Gene Regulatory Networks
  • Genetic Association Studies
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Protein Processing, Post-Translational

Substances

  • MicroRNAs

Grants and funding

We declare that the funds or sources of support received in this specific internal report study of Simón Bolívar University, Barranquilla, Colombia, and external funding by the Administrative Department of Science, Technology and Innovation of Colombia - COLCIENCIAS, subsidy 125380763038 to ENQ and 125380763188 to GAM. We clarified that the funder had no role in the design of the study, the collection and analysis of data, the decision to publish or the preparation of the manuscript.