MicroRNAs 221 and 222 bypass quiescence and compromise cell survival
Authors
Medina, Ricardo F.Zaidi, Sayyed K.
Liu, Chang-Gong
Stein, Janet L.
Van Wijnen, Andre J.
Croce, Carlo M.
Stein, Gary S.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2008-04-17Keywords
Blotting, NorthernBrain Neoplasms
Cell Cycle
Cell Division
Cell Line, Tumor
Cell Survival
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma
Humans
MicroRNAs
Protein Biosynthesis
RNA, Messenger
Cell Biology
Metadata
Show full item recordAbstract
MicroRNAs (miRNA) have tumor suppressive and oncogenic potential in human cancer, but whether and how miRNAs control cell cycle progression is not understood. To address this question, we carried out a comprehensive analysis of miRNA expression during serum stimulation of quiescent human cells. Time course analyses revealed that four miRNAs are up-regulated and >100 miRNAs are down-regulated, as cells progress beyond the G(1)-S phase transition. We analyzed the function of two up-regulated miRNAs (miR-221 and miR-222) that are both predicted to target the cell growth suppressive cyclin-dependent kinase inhibitors p27 and p57. Our results show that miR-221 and miR-222 both directly target the 3' untranslated regions of p27 and p57 mRNAs to reduce reporter gene expression, as well as diminish p27 and p57 protein levels. Functional studies show that miR-221 and miR-222 prevent quiescence when elevated during growth factor deprivation and induce precocious S-phase entry, thereby triggering cell death. Thus, the physiologic up-regulation of miR-221 and miR-222 is tightly linked to a cell cycle checkpoint that ensures cell survival by coordinating competency for initiation of S phase with growth factor signaling pathways that stimulate cell proliferation.Source
Cancer Res. 2008 Apr 15;68(8):2773-80. Link to article on publisher's siteDOI
10.1158/0008-5472.CAN-07-6754Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26579PubMed ID
18413744Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-07-6754