Dysregulation of microRNA biogenesis machinery in cancer

Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):121-34. doi: 10.3109/10409238.2015.1117054. Epub 2015 Dec 1.

Abstract

MicroRNAs (miRNAs) are integral to the gene regulatory network. A single miRNA is capable of controlling the expression of hundreds of protein coding genes and modulate a wide spectrum of biological functions, such as proliferation, differentiation, stress responses, DNA repair, cell adhesion, motility, inflammation, cell survival, senescence and apoptosis, all of which are fundamental to tumorigenesis. Overexpression, genetic amplification, and gain-of-function mutation of oncogenic miRNAs ("onco-miRs") as well as genetic deletion and loss-of-function mutation of tumor suppressor miRNAs ("suppressor-miRs") are linked to human cancer. In addition to the dysregulation of a specific onco-miR or suppressor-miRs, changes in global miRNA levels resulting from a defective miRNA biogenesis pathway play a role in tumorigenesis. The function of individual onco-miRs and suppressor-miRs and their target genes in cancer has been described in many different articles elsewhere. In this review, we primarily focus on the recent development regarding the dysregulation of the miRNA biogenesis pathway and its contribution to cancer.

Keywords: Argonaute; DGCR8; Dicer; Drosha; TRBP; microRNA; post-translational modifications; pre-miRNA; pri-miRNA; processing; stability.

Publication types

  • Review

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • Neoplasms / genetics*
  • Protein Processing, Post-Translational
  • Ribonuclease III / genetics
  • Transcription, Genetic

Substances

  • Argonaute Proteins
  • MicroRNAs
  • DROSHA protein, human
  • Ribonuclease III