A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator

Sci Rep. 2015 Feb 12:5:8336. doi: 10.1038/srep08336.

Abstract

MiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets. In one cluster containing three miRNAs, miR-612, miR-661 and miR-940, the annotated functions of the co-regulated genes suggested a role in small GTPase signalling. Although the three members of this cluster targeted the same subset of predicted genes, we showed that their overexpression impacted cell fates differently. miR-661 demonstrated enhanced phosphorylation of myosin II and an increase in cell invasion, indicating a possible oncogenic miRNA. On the contrary, miR-612 and miR-940 inhibit phosphorylation of myosin II and cell invasion. Finally, expression profiling in human breast tissues showed that miR-940 was consistently downregulated in breast cancer tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics*
  • Actin Cytoskeleton / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Movement / genetics
  • Cell Proliferation
  • Computational Biology / methods
  • Databases, Nucleic Acid
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • Monomeric GTP-Binding Proteins / metabolism
  • Signal Transduction

Substances

  • MIRN940 microRNA, human
  • MicroRNAs
  • Monomeric GTP-Binding Proteins