Title:Exploring Mechanisms of MicroRNA Downregulation in Cancer
Volume: 6
Issue: 1
Author(s): Marissa Williams, Yuen Y. Cheng, Cherie Blenkiron and Glen Reid*
Affiliation:
- Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia, Sydney Medical School, The University of Sydney, Sydney, NSW 2006,Australia
Keywords:
Cancer, epigenetic, genomic, microRNA biogenesis, microRNA downregulation, microRNA, processing, transcription.
Abstract: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression at a posttranscriptional
level. Each miRNA controls the expression of multiple messenger RNAs (mRNAs) and
their dysregulation has been implicated in multiple cancer phenotypes. While some miRNAs are
upregulated, global downregulation of miRNA expression is often the rule in cancer. A multitude of
potential mechanisms drive aberrant miRNA expression in cancer; miRNA coding regions can harbour
genomic defects including mutations, amplifications or deletions, and some miRNAs are broadly repressed
by transcription factors such as Myc or have epigenetic modifications to their promoter regions
such as hypermethylation of CpG islands. Additionally, the suppression of components of the miRNA
processing machinery has been shown to reduce mature miRNA expression and contribute to the malignant
phenotype. Understanding the mechanisms driving miRNA downregulation is important in uncovering
the critical and complex role of miRNAs in cancer biology. This review will outline the multiple
mechanisms by which cancer cells suppress miRNA expression.
