Pathway analysis of cancer-associated microRNA targets

Int J Oncol. 2012 Dec;41(6):2213-26. doi: 10.3892/ijo.2012.1658. Epub 2012 Oct 11.

Abstract

Carcinogenesis is a multi-step process, which includes oncogene activation, mutation silencing of tumor suppressor genes, impairment of chromosomes or epigenetic changes such as CpG island methylation through various cellular pathways, involving a series of somatic genetic alterations. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis. This study investigated eleven miRNAs previously identified as cancer-related regulators. Using function and pathway analysis of their targeted genes, the relevance of miRNA regulation in the induction of cancer can be observed. The results showed that CA-miRNAs may function in the post-transcriptional level mainly through manipulating the expression of transcription factors and protein kinases, and target genes for the CA-miRNAs were most prominently predicted to function in the regulation of transcription. Our analysis also highlighted the potential of these CA-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause a cancer cell mainly through five canonical pathways. Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes. These findings should form a useful knowledge base for potential future development of novel therapeutic treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Molecular Sequence Annotation
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Signal Transduction*

Substances

  • MicroRNAs