Control of MicroRNA-21 expression in colorectal cancer cells by oncogenic epidermal growth factor/Ras signaling and Ets transcription factors

Hanna B. Kern, Brian F. Niemeyer, Janet K. Parrish, Carol A. Kerr, Nasser K. Yaghi, Jason D. Prescott, Arthur Gutierrez-Hartmann, Paul Jedlicka

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRs) are important regulators of gene expression in normal physiology and disease, and are widely misexpressed in cancer. A number of studies have identified miR-21 as an important promoter of oncogenesis. However, as is true of most miRs, the mechanisms behind the aberrant expression of miR-21 in cancer are poorly understood. Herein, we examine the regulation of miR-21 expression in colorectal cancer (CRC) cells by the oncogenic epidermal growth factor (EGF)/Ras pathway and by Ets transcription factors, modulators of epithelial oncogenesis that are frequently misexpressed in CRC. We show that EGF/Ras efficiently induces the miR-21 primary transcript, but this does not rapidly and simply translate into higher mature miR-21 levels. Rather, induction of mature miR-21 by constitutive activation of this pathway is slow, is associated with only minimal activation of mitogen-activated protein kinase, and may involve stimulation of post-transcriptional processing by mechanisms other than Dicer stabilization. We further identify Ets transcription factors as modifiers of miR-21 expression in CRC. The effects of Ets factors on miR-21 expression are cell context-dependent, and appear to involve both direct and indirect mechanisms. The Ets factor Pea3 emerges from our studies as a consistent repressor of miR-21 transcription. Overall, our studies identify a complex relationship between oncogenic pathways and steady-state miR-21 levels in CRC, and highlight the need for greater understanding of the control of miR expression in cancer and other disease states.

Original languageEnglish (US)
Pages (from-to)1403-1411
Number of pages9
JournalDNA and Cell Biology
Volume31
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this