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Updated: May 11, 2026

Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells

Published on: September 28, 2011

RAS is regulated by the let-7 microRNA family

Steven M Johnson1, Helge Grosshans, Jaclyn Shingara

  • 1Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.

Cell
|March 16, 2005
PubMed

Insights

The let-7 microRNA family regulates RAS gene expression in both worms and humans. Lower let-7 levels in human lung tumors correlate with higher RAS protein, suggesting a role in cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression in eukaryotes.
  • The let-7 miRNA family plays a crucial role in developmental processes, including cell differentiation.
  • RAS genes are frequently mutated in human cancers and are involved in cell growth and proliferation.

Purpose of the Study:

  • To investigate the regulatory relationship between the let-7 miRNA family and the RAS pathway.
  • To determine if let-7 directly targets RAS genes in both model organisms and humans.
  • To explore the potential role of let-7 and RAS in the context of lung cancer.

Main Methods:

  • Reporter gene assays to assess let-7-mediated regulation of let-60/RAS.
  • Analysis of let-7 family member expression during C. elegans development.
  • Examination of let-7 and RAS expression levels in human lung tumor tissues.

Main Results:

  • The let-7 family was shown to negatively regulate let-60/RAS in C. elegans.
  • Multiple let-7 complementary sites (LCSs) were identified in the 3'UTR of let-60/RAS, mediating let-7-dependent repression.
  • Human RAS gene 3'UTRs also contain LCSs, indicating conserved let-7 regulation.
  • Reduced let-7 expression and elevated RAS protein levels were observed in human lung tumors.

Conclusions:

  • The let-7 miRNA family directly represses RAS gene expression through conserved mechanisms.
  • Dysregulation of the let-7-RAS axis, with decreased let-7 and increased RAS, is implicated in human lung tumorigenesis.
  • This study provides a molecular link between let-7 function and cancer development.

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