The role of miR-125b in T lymphocytes in the pathogenesis of systemic lupus erythematosus

Clin Exp Rheumatol. 2013 Mar-Apr;31(2):263-71. Epub 2013 Jan 9.

Abstract

Objectives: This study aimed to explore miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and the potential biological functions of the associated miRNA in the pathogenesis of SLE.

Methods: Fifty patients with active SLE and 26 healthy controls were enrolled. Four patients and four controls were used for miRNA microarray analysis to detect the levels of 847 miRNAs in PBMCs. The others were used for qRT-PCR confirmation and miRNA functional studies. A reporter gene assay was used to determine the biological function of miR-125b.

Results: Eleven miRNAs were found to be up-regulated and 26 miRNAs were down-regulated in SLE patients. Further analysis showed that the down-regulation of miR-125b, mainly in T cells, was negatively correlated with lupus nephritis. We also confirmed that ETS1 and STAT3 are target genes of miR-125b using a dual-luciferase reporter transfection assay.

Conclusions: These data identified this miRNA expression profile as a possible new biomarker of SLE. Moreover, the down-regulation of miR-125b mainly in T cells may contribute to the pathogenesis of SLE by regulating ETS1 and STAT3 gene expression.

MeSH terms

  • 3' Untranslated Regions
  • Case-Control Studies
  • Down-Regulation
  • Gene Expression Profiling / methods
  • Genes, Reporter
  • Genetic Markers
  • HEK293 Cells
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / immunology
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transfection

Substances

  • 3' Untranslated Regions
  • ETS1 protein, human
  • Genetic Markers
  • MIRN125 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Protein c-ets-1
  • STAT3 Transcription Factor
  • STAT3 protein, human