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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways

C Oneyama1, J Ikeda, D Okuzaki

  • 1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. coneyama@biken.osaka-u.ac.jp

Oncogene
|March 9, 2011
PubMed

Insights

c-Src activation in cancer downregulates miR-99a, a microRNA targeting mTOR and FGFR3. Restoring miR-99a inhibits tumor growth, revealing a key pathway for cancer control.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The tyrosine kinase c-Src is frequently upregulated in human cancers, contributing to tumor growth through incompletely understood mechanisms.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in cancer development.

Purpose of the Study:

  • To investigate the role of microRNAs in c-Src-mediated tumor growth.
  • To identify specific miRNAs regulated by c-Src and their downstream targets involved in tumorigenesis.

Main Methods:

  • Microarray profiling to identify miRNAs downregulated by c-Src activation.
  • Functional studies involving miRNA re-expression and target gene (mTOR, FGFR3) manipulation in cancer cells.
  • Analysis of miR-99a expression and its association with mTOR/FGFR3 in human lung cancer tissues.

Main Results:

  • c-Src activation leads to the downregulation of specific miRNAs, including miR-99a.
  • miR-99a directly targets and inhibits oncogenic mammalian target of rapamycin (mTOR) and fibroblast growth factor receptor 3 (FGFR3).
  • Re-expression of miR-99a suppressed tumor growth in c-Src-transformed cells, an effect reversed by mTOR overexpression. Downregulation of miR-99a was also observed in EGF- and Ras-transformed cells, and linked to mTOR/FGFR3 upregulation in lung cancers.

Conclusions:

  • The miR-99a/mTOR/FGFR3 pathway is a critical regulator of tumor growth in cancers with activated Src-related oncogenic pathways.
  • miR-99a acts as a tumor suppressor by targeting key oncogenic drivers like mTOR and FGFR3.
  • Targeting this miRNA pathway holds therapeutic potential for various human cancers.

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