WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia.
MicroRNAs are short single-stranded RNAs that regulate target gene expression by binding to complementary sites in the 3' untranslated region (UTR) of their mRNA targets. The polycistronic miR-17-92 cluster, which encodes miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a, was previously shown to be overexpressed in multiple types of cancer. In this study, target gene prediction algorithms were used to predict potential targets of the miR-17-92 cluster. WEE1, a kinase that inhibits cell cycle progression, was identified as a possible target of five of the six miRNAs in the cluster. Luciferase reporter assays were used to determine that miR-17, miR-20a, and miR-18a specifically target nucleotides 465-487 of the 3' UTR of WEE1, whereas miR-19a and miR-19b exert control on WEE1 by targeting nucleotides 1069-1091. A negative correlation was determined between endogenous miR-17 or miR-19a expression and endogenous WEE1 protein expression in the same panel of cell lines. We conclude that WEE1 is a valid target of the miR-17-92 cluster in leukemia.
Molecular Biology Program, Loyola University Chicago, Maywood, IL, USA.
Sonia
S
Brockway
Department of Medicine, Loyola University Chicago, Maywood, IL, USA. Electronic address: nzelezn@luc.edu.
Nancy J
NJ
Zeleznik-Le
D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D062085:RNA, Long Noncoding
D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C568997:MIR17HG, human; C524941:MIRN17 microRNA, human; C522576:MIRN18A microRNA, human; C549214:MIRN19A microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human
MicroRNA; WEE1; kinase; leukemia; miR-17-92