roRNA miR-302 Inhibits the Tumorigenecity of Human ipotent Stem Cells by Coordinate Suppression of the

nloaded -302 is the major microRNA found in human embryonic stem cells and induced pluripotent stem cells, function has been unclear. In mice, there is evidence that miR-302 may silence p21Cip1 (CDKN1A) to te cell proliferation, whereas studies in human reprogrammed pluripotent stem cells suggested that ed miR-302 expression inhibited cell cycle transit. Here, we clarify this difference, reporting that in cells, miR-302 simultaneously suppressed both the cyclin E-CDK2 and cyclin D-CDK4/6 pathways to >70% of the G1-S cell cycle transition. Concurrent silencing of BMI-1, a cancer stem cell marker targeted R-302, further promoted tumor suppressor functions of p16Ink4a and p14/p19Arf directed against /6–mediated cell proliferation. Among all G1 phase checkpoint regulators, human p21Cip1 was found be a valid target of miR-302. Overall, our findings indicate that miR-302 inhibits human pluripotent not to stem cell tumorigenicity by enhancing multiple G1 phase arrest pathways rather than by silencing p21Cip1. Cancer Res; 70(22); 9473–82. ©2010 AACR.