Primate-specific miR-944 activates p53-dependent tumor suppression in human colorectal cancers

Abstract

As cancers with a high incidence rate, colorectal cancers are a main cause of cancer-related death. MicroRNAs are often deregulated in cancers. The primate-specific miR-944, located in a p63 intron, is known to be highly expressed in patients exhibiting low colorectal cancer recurrence rates. However, the biological functions of miR-944 in colorectal cancers remain unclear. In this study, we found that miR-944 was downregulated in colorectal cancer tissues, and inhibited cancer cell growth in a xenograft mouse model. The overexpression of miR-944 caused G1 phase arrest and increased p53 expression in cancer cells. p53 stability was enhanced by miR-944s targeting E3 ligases COP1 and MDM2. Overexpression of COP1 and MDM2 restored cell growth inhibition caused by miR-944. Taken together, our results suggest that miR-944 acts as a potential tumor suppressor in colorectal cancers through the ubiquitin-proteasome system.

Keywords: Colorectal cancer; Primate specific miRNA; Tumor suppressor; miR-944; p53.