Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

Nat Commun. 2011 Nov 22;2:554. doi: 10.1038/ncomms1555.

Abstract

miRNA globally deregulates human carcinoma. A critical open question is how many miRNAs functionally participate in cancer development, particularly in metastasis. We systematically evaluate the capability of all known human miRNAs to regulate certain metastasis-relevant cell behaviours. To perform the high-throughput screen of miRNAs, which regulate cell migration, we developed a novel self-assembled cell microarray. Here we show that over 20% of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. MiR-23b, which is downregulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including tumour growth, invasion and angiogenesis in vivo. It regulates a cohort of prometastatic targets, including FZD7 or MAP3k1. These findings provide new insight into the physiological and potential therapeutic importance of miRNAs as a new class of functional modulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • HCT116 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • In Vitro Techniques
  • MAP Kinase Kinase Kinase 1 / genetics
  • MAP Kinase Kinase Kinase 1 / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasms / genetics
  • Neoplasms / metabolism*

Substances

  • FZD7 protein, human
  • Frizzled Receptors
  • MicroRNAs
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human