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

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> miR-944 was downregulated in colorectal cancer tissues. </LI> <LI> The overexpression of miR-944 caused G1 phase arrest in cancer cells. </LI> <LI> miR-944 stimulated p53-mediated signaling by increasing p53 stability. </LI> <LI> COP1 and MDM2 are functional targets of miR-944 mediating its anti-proliferative effect in colorectal cancers. </LI> </UL> </P>