Expression levels of NF-Y target genes changed by CDKN1B correlate with clinical prognosis in multiple cancers.
CDK inhibitors CDKN1B (p27) and CDKN2A (p16) inhibit cell cycle progression. A lower expression level of only p27 has been correlated with poorer prognosis in various types of clinical cancers. The difference may be the result of distinct genes downstream of these CDK inhibitors. Here, we report that NF-Y transcription factor-targeted genes specifically down-regulated by p27 correlate with poor prognosis in multiple tumor types. We performed mRNA expression profiling in HCT116 cells over-expressing either p16 or p27 and identified their regulatory genes. In silico transcription factor prediction indicated that most of the genes specifically down-regulated by p27 are controlled by NF-Y. Under the hypothesis that NF-Y-targeted genes are responsible for poor prognosis, we predicted prognosis in four types of cancer based on genes with the NF-Y motif, and found a significant association between the expression of NF-Y-targeted genes and poor prognosis.
Yamanaka
Kazunori
K
Department of Cancer Research, Banyu Tsukuba Research Institute, Merck Research Laboratory, Tsukuba, Ibaraki 300-2611, Japan.
Mizuarai
Shinji
S
Eguchi
Tomohiro
T
Itadani
Hiraku
H
Hirai
Hiroshi
H
Kotani
Hidehito
H
D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D023081:CCAAT-Binding Factor; C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27