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

DNA and Cell Biology
H B KernP Jedlicka

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 mechani...Continue Reading

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Citations

Jul 3, 2013·Journal of Cancer Research and Clinical Oncology·Jitka MlcochovaOndrej Slaby
May 1, 2015·Molecular Cancer·Yingjie YuAdhip P N Majumdar
Feb 11, 2015·World Journal of Gastroenterology : WJG·Bo GongZi-Jun Li
Apr 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haojie ZhuTing Yang
Sep 1, 2021·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Kun DongZhiwei Zhang

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Methods Mentioned

BETA
PCR
transfections
transfection
Assay
electrophoresis

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