Modulation of microRNA processing by 5-lipoxygenase

FASEB J. 2021 Feb;35(2):e21193. doi: 10.1096/fj.202002108R. Epub 2020 Nov 17.


The miRNA biogenesis is tightly regulated to avoid dysfunction and consequent disease development. Here, we describe modulation of miRNA processing as a novel noncanonical function of the 5-lipoxygenase (5-LO) enzyme in monocytic cells. In differentiated Mono Mac 6 (MM6) cells, we found an in situ interaction of 5-LO with Dicer, a key enzyme in miRNA biogenesis. RNA sequencing of small noncoding RNAs revealed a functional impact, knockout of 5-LO altered the expression profile of several miRNAs. Effects of 5-LO could be observed at two levels. qPCR analyses thus indicated that (a) 5-LO promotes the transcription of the evolutionarily conserved miR-99b/let-7e/miR-125a cluster and (b) the 5-LO-Dicer interaction downregulates the processing of pre-let-7e, resulting in an increase in miR-125a and miR-99b levels by 5-LO without concomitant changes in let-7e levels in differentiated MM6 cells. Our observations suggest that 5-LO regulates the miRNA profile by modulating the Dicer-mediated processing of distinct pre-miRNAs. 5-LO inhibits the formation of let-7e which is a well-known inducer of cell differentiation, but promotes the generation of miR-99b and miR-125a known to induce cell proliferation and the maintenance of leukemic stem cell functions.

Keywords: 5-lipoxygenase; Dicer; cancer; inflammation; leukotriene; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Cell Line, Tumor
  • Down-Regulation
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Processing, Post-Transcriptional*
  • Ribonuclease III / metabolism
  • Transcriptome


  • MicroRNAs
  • Arachidonate 5-Lipoxygenase
  • Ribonuclease III