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. 2011 Dec 20;287(8):5979–5987. doi: 10.1074/jbc.M111.297937

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© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 4. — Up-regulation of key cell cycle regulators and apoptosis in the yolk sac of GW182^gt/gt embryos at E9.5. A, highly expressed in yolk sac, levels of miR-17/106 family members are not altered in GW182^gt/gt mutant. B, miRNAs highly expressed in yolk sac with the same seed sequence. C, miR-17/106 is expressed in both endoderm and mesoderm of yolk sac with selectively enriched expression in endoderm; expression of mir-126–3p is mainly in the mesoderm, whereas miR-451 is in hematopoietic cells of blood island. D, mRNA levels of targets of miR-17/106/93 and miR-25/92, such as p21, p57, Lats1/2, and Rb, are significantly increased in GW182^gt/gt yolk sac, as assayed by Affymetrix mRNA array (p < 0.05 for all these genes). E, Western blot detected a significant increase in P21 and cleaved caspase 3 levels in the yolk sac of GW182^gt/gt embryos at E9.5. F, increased P21 in the yolk sac endoderm of GW182^gt/gt embryos was detected by immunostaining. G, model of GW182 function in miRNA-mediated gene silencing in the yolk sac.