MicroRNAs

Critical regulators of development, cellular physiology and malignancy

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability or translational efficiency of target mRNAs. These regulatory RNAs function by acting as sequence-specific guides which recruit a large protein complex known as the RNA-induced silencing complex, or RISC, to target mRNAs which are subsequently silenced. Diverse functions have been attributed to miRNAs including the regulation of cellular differentiation, proliferation, and apoptosis. Moreover, significant evidence has accumulated implicating a fundamental role for miRNAs in the development of cancer. We recently demonstrated that the oncogenic transcription factor c-Myc regulates a group of miRNAs known as the mir-17 cluster. This represents the first documented example of a mammalian transcription factor that regulates miRNA expression. Moreover, it was independently demonstrated that the mir-17 cluster accelerates c-Myc-induced lymphoma-genesis in an in vivo mouse model. Together, these studies support an important role for this group of miRNAs in c-Myc-mediated tumorigenesis. We have also demonstrated that two miRNAs in this cluster regulate the pro-proliferative, pro-apoptotic transcription factor E2F1. Herein, we propose a model in which the mir-17 cluster prevents excessive E2F1 activity, and thereby apoptosis, in response to activation of c-Myc.

Original languageEnglish (US)
Pages (from-to)1179-1184
Number of pages6
JournalCell Cycle
Volume4
Issue number9
StatePublished - Sep 2005

Fingerprint

Physiology
MicroRNAs
Neoplasms
Transcription Factors
E2F1 Transcription Factor
RNA-Induced Silencing Complex
RNA
Apoptosis
Messenger RNA
Reduced instruction set computing
Lymphoma
Carcinogenesis
Nucleotides
Chemical activation
Cell Proliferation
Molecules
Proteins

Keywords

  • Cancer
  • E2F1
  • microRNA
  • mir-17 cluster
  • Myc
  • Post-transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

MicroRNAs : Critical regulators of development, cellular physiology and malignancy. / Mendell, Joshua T.

In: Cell Cycle, Vol. 4, No. 9, 09.2005, p. 1179-1184.

Research output: Contribution to journalArticle

@article{b9a4854f88df4734b08a0083e98c03c2,
title = "MicroRNAs: Critical regulators of development, cellular physiology and malignancy",
abstract = "MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability or translational efficiency of target mRNAs. These regulatory RNAs function by acting as sequence-specific guides which recruit a large protein complex known as the RNA-induced silencing complex, or RISC, to target mRNAs which are subsequently silenced. Diverse functions have been attributed to miRNAs including the regulation of cellular differentiation, proliferation, and apoptosis. Moreover, significant evidence has accumulated implicating a fundamental role for miRNAs in the development of cancer. We recently demonstrated that the oncogenic transcription factor c-Myc regulates a group of miRNAs known as the mir-17 cluster. This represents the first documented example of a mammalian transcription factor that regulates miRNA expression. Moreover, it was independently demonstrated that the mir-17 cluster accelerates c-Myc-induced lymphoma-genesis in an in vivo mouse model. Together, these studies support an important role for this group of miRNAs in c-Myc-mediated tumorigenesis. We have also demonstrated that two miRNAs in this cluster regulate the pro-proliferative, pro-apoptotic transcription factor E2F1. Herein, we propose a model in which the mir-17 cluster prevents excessive E2F1 activity, and thereby apoptosis, in response to activation of c-Myc.",
keywords = "Cancer, E2F1, microRNA, mir-17 cluster, Myc, Post-transcriptional regulation",
author = "Mendell, {Joshua T.}",
year = "2005",
month = "9",
language = "English (US)",
volume = "4",
pages = "1179--1184",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - MicroRNAs

T2 - Critical regulators of development, cellular physiology and malignancy

AU - Mendell, Joshua T.

PY - 2005/9

Y1 - 2005/9

N2 - MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability or translational efficiency of target mRNAs. These regulatory RNAs function by acting as sequence-specific guides which recruit a large protein complex known as the RNA-induced silencing complex, or RISC, to target mRNAs which are subsequently silenced. Diverse functions have been attributed to miRNAs including the regulation of cellular differentiation, proliferation, and apoptosis. Moreover, significant evidence has accumulated implicating a fundamental role for miRNAs in the development of cancer. We recently demonstrated that the oncogenic transcription factor c-Myc regulates a group of miRNAs known as the mir-17 cluster. This represents the first documented example of a mammalian transcription factor that regulates miRNA expression. Moreover, it was independently demonstrated that the mir-17 cluster accelerates c-Myc-induced lymphoma-genesis in an in vivo mouse model. Together, these studies support an important role for this group of miRNAs in c-Myc-mediated tumorigenesis. We have also demonstrated that two miRNAs in this cluster regulate the pro-proliferative, pro-apoptotic transcription factor E2F1. Herein, we propose a model in which the mir-17 cluster prevents excessive E2F1 activity, and thereby apoptosis, in response to activation of c-Myc.

AB - MicroRNAs (miRNAs) are 18-24 nucleotide RNA molecules that regulate the stability or translational efficiency of target mRNAs. These regulatory RNAs function by acting as sequence-specific guides which recruit a large protein complex known as the RNA-induced silencing complex, or RISC, to target mRNAs which are subsequently silenced. Diverse functions have been attributed to miRNAs including the regulation of cellular differentiation, proliferation, and apoptosis. Moreover, significant evidence has accumulated implicating a fundamental role for miRNAs in the development of cancer. We recently demonstrated that the oncogenic transcription factor c-Myc regulates a group of miRNAs known as the mir-17 cluster. This represents the first documented example of a mammalian transcription factor that regulates miRNA expression. Moreover, it was independently demonstrated that the mir-17 cluster accelerates c-Myc-induced lymphoma-genesis in an in vivo mouse model. Together, these studies support an important role for this group of miRNAs in c-Myc-mediated tumorigenesis. We have also demonstrated that two miRNAs in this cluster regulate the pro-proliferative, pro-apoptotic transcription factor E2F1. Herein, we propose a model in which the mir-17 cluster prevents excessive E2F1 activity, and thereby apoptosis, in response to activation of c-Myc.

KW - Cancer

KW - E2F1

KW - microRNA

KW - mir-17 cluster

KW - Myc

KW - Post-transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=25444457833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444457833&partnerID=8YFLogxK

M3 - Article

VL - 4

SP - 1179

EP - 1184

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 9

ER -