qRT-PCR analysis confirmed that the mRNA levels of cyclin family members ( ccna1 , ccnb1
, ccnd1 , and cdk1 ), minichromosome maintenance proteins ( cdc45 , mcm2 , mcm3 , mcm4 , mcm5 , mcm6 , and mcm7 ), and proliferation cell nuclear antigen ( PCNA ) were significantly upregulated in ATF3-overexpressing CFs [Figure 3]a.
Three genes whose expression had been significantly elevated by EBV were cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1
), and survivin ; this finding in addition to our knowledge about survivin implication in cancer indicates that its application for graft promotion should be cautiously studied to avoid inducing malignancies.
It was found that expression of TP53 (HR 1.9, p = 31 x [10.sup.-7]) was associated with worse overall survival (OS) for glioma patients, as well as TOP2A (HR 4.4, p = 0), CDK1 (HR 4.8, p = 0), CCNB1
(HR 5.9, p = 0), CDC20 (HR 5.2, p = 0), CCNA2 (HR 5.1, p = 0), NDC80 (HR 5.8, p = 0), AURKA (HR 5.3, p = 0), BIRC5 (HR 5, p = 0), CCNB2 (HR 5.4, p = 0), KIF11 (HR 2.3, p = 15 x [10.sup.-10]), and MAD2L1 (HR 4.4, p = 0), while expression of PHLPP2 (HR 0.41, p = 1.3x [10.sup.-11]), DLG4 (HR 0.59, p = 35 x [10.sup.-5]), and MYC (HR 0.58, p = 2.1 x [10.sup.-5]) was associated with better overall survival (OS) for glioma patients (Figure 3).
Module Pa Size Gene Pathway Pg 1 0.042 6 NCAPG, CDC45, OIP5, Cell 0.004 RAD51AP1, CDCA3, TRIP13 division 3 0.047 5 CCNB1
, NCAPG, NDC80, Cell 0.001 CDCA3, NCAPH division [P.sub.a]: P-value for attractor module, [P.sub.g]: P-value for gene ontology bioprocess.
Genes included in cluster 4 and 13 were related to cell cycle and renewal of stem cells (CCNB1
, CCNA2, FGF7, MAP2K4, WNT5A, KITGL, and FGF5).
The cancer genes are comprised of a proliferation set (5 genes: Ki67, STK15, Survivin, CCNB1
, MYBL2), estrogen hormone receptor genes (5 genes: ER, PGR, BCL2, SCUBE2), HER2neu set (2 genes: GRB7, HER2), invasion set (2 genes: MMP11, CTSL2), and GSTM-1 (1 gene).
The PPI network consisting of induced genes (Figure 3(a)) contained a large cell cycle-related cluster with hubs and nodes related to S-phase (CCNB1
and CCNB2, CCND3, CDC16, MCM3, MCM7, and CDC25) and chromosome separation (PLK1, ANAPC5, 7, CDC20, and TUBA1A).
Of the PLC samples, we found that the transcriptional expressions of MLH3, ACSL6, CD55, CR1, PDE3B, CCNB1
, PAICS, SEC62, BIRC3, TCF7, NT5E, and PSPH in the PBMCs of gan-shen Yin deficiency group were significantly lower than those in non-gan-shen Yin deficiency group (Figure 1(a), p < 0.05).
Overexpression of cyclin-dependent kinases (CDKs) and cyclin proteins (CCND1, CCNE1, and CCNB1
) are found in many human cancers .
Os 16 genes incluem aqueles relacionados ao RE (ER, PR, BCL2 e SCUBE2), proliferacao (Ki67, STK15, Survivin, CCNB1
e MYBL2), HER2 (HER2 e GRB7), invasao (MMP11 e CTSL2), alem de tres genes adicionais relacionados (GSTM1, CD68 e BAG1).
The mRNA expression of cytoplasm maturation marker genes (MOS, BMP15, GDF9, and CCNB1
) was analyzed by real-time RT-PCR (Figure 3B).
Gene ontology: biological Genes p-Value process terms Cell cycle CCNB1
, CCNB2, MNAT1, CDC2, 2.7 E-14 CDKN 1 A, CDKN3, CDKN2A, ANAPC1, CDK10 Cellular metabolism KRT15, KIF1B, ZNF697, 4.3E-13 PRG2, P2RY2,IMMP2L Growth factor and growth BMP-2, TCF[beta]1, VEGF, 1.2E-11 factor receptor activity BMP8B, CSF1, FCFR1, BMPR2, 1GF2R, PDCFB, TGFBR2, NRP1, CCR2 Biosynthetic process CEL, COL11A2, ACPP, MMP14, 1.8E-9 CACNB1, ALPL, CDH1, ITGA3, SERPINB10, TAF4B, ABCB10, IRF8 Cell proliferation ATF3, MK167, S100A6, FTH1, DHCR7 2.1E-8 Signal transduction MAP2K3, MAPK14, MAP3K10, BAMBI, NDRG2, ECM1, SMAD7 5.5E-7 Apoptosis MYC, P53AIP1, ZBTB16, BBC3, 1.3E-5 VHL, CASP3, APITD1 Table 5 KEGG pathway analysis.