Post‐transcriptional regulation of the tumor suppressor miR‐139‐5p and a network of miR‐139‐5p‐mediated mRNA interactions in colorectal cancer
Citations Over TimeTop 10% of 2014 papers
Abstract
MicroRNAs play key roles in many biological processes, and are frequently dysregulated in tumor cells. However, there are few studies on how microRNAs are dysregulated. miR-139-5p, an important tumor suppressor, is often underexpressed in gastrointestinal cancer cells. Here, we describe post-transcriptional regulation of this intronic microRNA in human colorectal cancer. miR-139-5p is expressed independently of its overexpressed host gene PDE2A in colorectal cancer tissues and cell lines. The miR-139-5p target genes IGF1R, ROCK2 and RAP1B exert regulatory effects on the miR-139-5p expression level, relying on their ability to compete for miR-139-5p binding. These overexpressed target genes also regulate each others' protein levels through 3'-UTRs, thus regulating tumor cell growth and motility properties. Our study provides a mechanistic, experimentally validated rationale for intronic microRNA dysregulation in colorectal cancer, revealing novel oncogenic roles of IGF1R, ROCK2 and RAP1B 3'-UTRs.
Related Papers
- → Posttranscriptional Regulation of MicroRNA Biogenesis in Animals(2010)573 cited
- → Novel regulation and functional interaction of polycistronic miRNAs(2015)61 cited
- → Expression levels of microRNAs are not associated with their regulatory activities(2011)21 cited
- → Progress of microRNA-29b in tumors(2017)
- → Hu antigen R and Tristetraprolin: Regulates Claudin 1 mRNA Stability in Colon Cancer(2012)