The statistics of genes regulated by the transcription factors in Figure 2 also showed that the target genes regulated by more than 3 transcription factors were IL-6, MAPK14
, RELA, and FOS; JUN was also regulated by the 2 transcription factors.
Gene Full name Description Degree MAPK14
Mitogen-activated Down 68 protein kinase 14 ESR1 Estrogen receptor 1 Up 54 PTEN Phosphatase and Down 52 tensin homolog MTOR Mechanistic target Up 40 of rapamycin ATM ATM serine/threonine Up 35 kinase ICAM1 Intercellular Down 33 adhesion molecule 1 CD40 CD40 molecule Up 32 AURKA Aurora kinase A Down 31 PRKDC Protein kinase, DNA-activated, Down 29 catalytic polypeptide TK2 Thymidine kinase 2, Up 29 mitochondrial Degree was used for describing the importance of protein nodes in network.
While other proteins (GSK3B, POU5F1, MAPK14
, CREB1, SOX2, KLF4, PRKACA, MAPK10, STAT1, ACTB, TUBB3, MYC, GAPDH, AKT1, and CTNNB1) are related with process of aging, neuronal diseases, cardiovascular diseases, abnormal brain development, mental retardation, schizophrenia, and mycobacterial and viral infections [60-62].
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.
In fact it appears that MAPK12 (p38[gamma]) arose from a tandem duplication of MAPK11 (p38[beta]) on chromosome 22 while MAPK14
(p38[alpha]) and MAPK13 (p38[delta]) subsequently resulted from a single segmental duplication of the MAPK11-MAPK12 gene unit on chromosome 6 .
At the time, no drugs existed that could act against MAPK13, but several were able to inhibit a similar enzyme, MAPK14
MAP2K3 is a MAP kinase kinase family member that could potentially function as an oncogene by phosphorylating and activating p38 MAPK and MAPK14
. Our query of a previous array data restricted to 17q11 (45) in conventional ACC shows that MAP2K3 is increased, as is HER2/neu, although to a lesser degree.
For instance, chrysin interacted not only with the genes directly related to inflammation, such as ALOX5, TLR4, MAPL10, MAPK14
, and MAPK2K4, but also with genes indirectly related to inflammation, such as HTR2A, HSP90AA1, and ADCY5.
Primers for human GAPDH, SOD1, SOD2, CAT, GPX1, CCS, PRDX6, FOXO3, CDKN2A, PAK2, TP53, MAPK14
, and JUN were designed by using GenBank database sequences and Primer 3 software  (http://bioinfo.ut.ee/primer3-0.4.0/).
The connectivity degree of certain genes exceeded 20, including DHX15, NDUFS3, PSMC6, UBE2C, EIF4G1, DHX9, PSMC3, and HNRNPA2B1 in the upregulated PPI network, and MAPK1, IL6, FN1, MAPK14
, STAT3, and VWF in the downregulated PPI network (Table 1).
Lastly, a DNA damage protein (Gadd45a) and a MAP kinase (Mapk14
), two other proteins recently associated with Wnt activation, were also differentially expressed in PB- and PTU-treated animals but not in NaI-treated animals (Hildesheim et al.
Furthermore, the system pharmacology study demonstrated that MAPK1/3 (ERK1/2), MAPK14
(p38), MAPK8 (JNK), and NF-[kappa]B were the predicted targets of BJF.