MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression.
microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.
Ivanovska
Irena
I
Rosetta Inpharmatics LLC, 401 Terry Ave. N, Seattle, WA 98109, USA. irena_ivanovska@merck.com
Ball
Alexey S
AS
Diaz
Robert L
RL
Magnus
Jill F
JF
Kibukawa
Miho
M
Schelter
Janell M
JM
Kobayashi
Sumire V
SV
Lim
Lee
L
Burchard
Julja
J
Jackson
Aimee L
AL
Linsley
Peter S
PS
Cleary
Michele A
MA
D001940:Breast / Q000166:cytology; D002453:Cell Cycle / Q000502:physiology*; D002461:Cell Line, Transformed / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D018816:Genes, cdc; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D004317:Doxorubicin