Progressing from Recurring Tissue Injury to Genomic Instability: A New Mechanism of Neutrophil Pathogenesis

Triet M. Bui, Ronen Sumagin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aberrant neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. While the genotoxic function of PMNs and its implications in carcinogenesis have been primarily associated with oxidative stress, recent work by Butin-Israeli and colleagues has defined a novel mechanism where PMN-derived microparticles through the delivery and activity of specific miRNAs promoted formation of double-strand breaks (DSBs), and in parallel, suppressed DSB repair through the downregulation of lamin B1 and Rad51. Respective downregulation of these two proteins compromised the nuclear envelope and high-fidelity repair by homologous recombination, increasing DSB accumulation and aneuploidy. This discovery defined a novel mode of action where PMN-mediated suppression of DSB repair leading to genomic instability in the injured mucosa may facilitate progression toward colorectal cancer.

Original languageEnglish (US)
Pages (from-to)747-753
Number of pages7
JournalDNA and Cell Biology
Volume38
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • IBD
  • carcinogenesis
  • inflammation
  • microRNAs
  • neutrophils
  • wound healing

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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