MicroRNA miR-302 Inhibits the Tumorigenecity of Human Pluripotent Stem Cells by Coordinate Suppression of the CDK2 and CDK4/6 Cell Cycle Pathways

S.-L. Lin, D. C. Chang, S.-Y. Ying, D. Leu, D. T. S. Wu
2010 Cancer Research  
miR-302 is the major microRNA found in human embryonic stem cells and induced pluripotent stem cells, but its function has been unclear. In mice, there is evidence that miR-302 may silence p21Cip1 (CDKN1A) to promote cell proliferation, whereas studies in human reprogrammed pluripotent stem cells suggested that elevated miR-302 expression inhibited cell cycle transit. Here, we clarify this difference, reporting that in human cells, miR-302 simultaneously suppressed both the cyclin E-CDK2 and
more » ... lin D-CDK4/6 pathways to block >70% of the G 1 -S cell cycle transition. Concurrent silencing of BMI-1, a cancer stem cell marker targeted by miR-302, further promoted tumor suppressor functions of p16Ink4a and p14/p19Arf directed against CDK4/6-mediated cell proliferation. Among all G 1 phase checkpoint regulators, human p21Cip1 was found not to be a valid target of miR-302. Overall, our findings indicate that miR-302 inhibits human pluripotent stem cell tumorigenicity by enhancing multiple G 1 phase arrest pathways rather than by silencing p21Cip1. Cancer Res; 70(22); 9473-82.
doi:10.1158/0008-5472.can-10-2746 pmid:21062975 fatcat:qu55shcwnneznbt5xiaa73stda