Increased UBE2L6 regulated by type 1 interferon as potential marker in TB

J Cell Mol Med. 2021 Dec;25(24):11232-11243. doi: 10.1111/jcmm.17046. Epub 2021 Nov 12.

Abstract

The aim of this study is to identify potential biomarker of tuberculosis (TB) and determine its function. Differentially expressed mRNAs(DEGs) were selected from a blood database GSE101805, and then, 30 key genes were screened using STING, Cytoscape and further functionally enriched. We then found that only 6 of 13 genes related to ubiquitination (the first in the functional enrichment) were increased significantly. ROC analysis showed that UBE2L6, among 6 genes, had the highest diagnostic value, and then, we found that it also had mild value in differential diagnosis. Moreover, our analysis showed that UBE2L6 may be upregulated by type I interferon, which was further confirmed by us. In addition, we also found that UBE2L6 inhibits the apoptosis of Mycobacterium tuberculosis(Mtb)infected macrophages. Subsequently, we discovered that miR-146a-5p, which may target UBE2L6, is reduced in peripheral blood mononuclear cells (PBMC) and plasma of TB, and it also had certain diagnostic efficiency(AUC=0.791). In brief, we demonstrated that UBE2L6 as well as miR-146a-5p is a potential biomarker for TB and UBE2L6,which may also plays important role in TB by, at least, modulating Mtb-infected macrophage apoptosis.

Keywords: UBE2L6; biomarker; miR-146a-5p; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Biomarkers*
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Host-Pathogen Interactions*
  • Humans
  • Interferon Type I / metabolism*
  • Mice
  • MicroRNAs / genetics
  • Models, Biological
  • Mycobacterium tuberculosis
  • RAW 264.7 Cells
  • RNA Interference
  • ROC Curve
  • Transcriptome
  • Tuberculosis / genetics*
  • Tuberculosis / metabolism*
  • Tuberculosis / microbiology
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Biomarkers
  • Interferon Type I
  • MicroRNAs
  • UBE2L6 protein, human
  • Ubiquitin-Conjugating Enzymes