MicroRNA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cells.
Human embryonic stem (ES) cells exhibit a shorter G(1) cell cycle phase than most somatic cells. Here, we examine the role of an abundant, human ES cell-enriched microRNA, miR-92b, in cell cycle distribution. Inhibition of miR-92b in human ES cells results in a greater number of cells in the G(1) phase and a lower number in the S phase. Conversely, overexpression of miR-92b in differentiated cells results in a decreased number of cells in G1 phase and an increased number in S-phase. p57, a gene whose product inhibits G(1) to S-phase progression, is one of the predicted targets of miR-92b. Inhibition of miR-92b in human ES cells increases p57 protein levels, and miR-92b overexpression in differentiated cells decreases p57 protein levels. Furthermore, miR-92b inhibits a luciferase reporter construct that includes part of the 3' untranslated region of the p57 gene containing the predicted target of the miR-92b seed sequence. Thus, we show that the miRNA miR-92b directly downregulates protein levels of the G(1)/S checkpoint gene p57. STEM CELLS 2009;27:1524-1528.
Sengupta
Srikumar
S
Morgridge Institute for Research, Madison, Wisconsin, USA.
Nie
Jeff
J
Wagner
Ryan J
RJ
Yang
Chuhu
C
Stewart
Ron
R
Thomson
James A
JA
D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008957:Models, Genetic; D016196:S Phase / Q000235:genetics*
C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D035683:MicroRNAs