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.
[1]E China Univ Sci & Technol, Dept Mol & Cellular Pharmacol, Biomed Nanotechnol Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China.
[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai, Peoples R China.
[4]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Respirat, Shanghai 200030, Peoples R China.
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