Endochondral Actin Focal TGF[beta] MAPK ossification cytoskeleton adhesion signaling signaling FGF2 FGF1 ITGA6 UCHL5 STMN1 TGFB2 FGF2 STYK1 CDC2 DUSP1 PLAT FGF5 CAV1 SMURF2 TRAF2 CALM1 FGF22 CAV2 NEDD9 BDNF ADAMTS1 KRAS CAV3 STAMBPL1 MAP3K5 OPG NRAS LAMC2 CCNB2 ACVR1C C11orf13 THBS1 RBL1 KRAS F2R PXN MAPK8 TGFB2 CRK RHOB PARD6A NRAS PAK1 PDPK1 CAV1 PPP5C ARHGEF7 MYLK2 TFDP1 PAK1 VIL2 PAK1 KLF6 CRK PXN MAPK8 FST MAPK8 BCL2 SERPINE1 CCND3
THBS1 CRK NOG HRAS Table 3: Genes involved in adipogenesis-related pathways that are upregulated in CYD-treated hMSCs.
Recently, cyclinD3 (CCND3
) was suggested to play an important role in B cell proliferation, development, and differentiation.
Translocations targeting CCND2, CCND3
, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.
miRNA-16 targets several cell cycle regulators, including cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin D3 (CCND3
), cyclin E1 (CCNE1), cyclin-dependent kinase-1 (CDK1), and cyclin-dependent kinase-6 (CDK6).
Additional recurrently mutated genes are also characterized by mutation hotspots in B-cell lymphomas, including myeloid differentiation primary response 88 (MYD88; L265P), CD79b molecule (CD79B; Y196C), or cyclin D3 (CCND3
; I290R) (13-15).
Based on target prediction programs (miRTarBase, TargetScan, miRanda, and MiRBase) and published papers, we found highly evidenced candidate target genes (hypoxia-inducible factor 1A and Cullin 2 genes for hypoxia and angiogenesis; cyclin-dependent kinase 6 (CDK6), Cyclin D1 (CCND1), Cyclin E1 (CCNE1), and CCND3
genes for cell cycle) of hsa-miR-424-5p.
Symbol Gene name 1 CCNA1 Cyclin A1 2 CCNA2 Cyclin A2 3 CCNB1 Cyclin B1 4 CCND1 Cyclin D1 5 CCND2 Cyclin D2 6 CCND3
Cyclin D3 7 CCNE1 Cyclin E1 8 CCNE2 Cyclin E2 9 CCNH Cyclin H 10 CDC25A Cell division cycle 25 homolog A (S.
In all, 54% of myeloma tumors overexpress cyclin D1 (CCND1), 48% overexpress cyclin D2 (CCND2), 3% overexpress cyclin D3 (CCND3
), and 8% overexpress both CCND1 and CCND2 (15).
Many of the genes differentially expressed by all four treatments (high dose), specifically Ccnd3
(Sasaki et al.
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).
(63) Carcinoma in situ has a high rate of TP53 mutations, (64) and the following genetic mutation rates have been reported for urothelial carcinoma: PIK3CA, 26%; CDKN2A/B, 23%; RB1, 17%; CCND1, 14%; FGFR1, 14%; CCND3
, 11%; FGFR3, 11%; MDM2, 11%; EGFR, 6%; and HER2/neu, 6%.65 Other genetic alterations have been identified in bladder carcinogenesis, including mutations in RAS gene family members and in TERT, as well as the loss of the RB1 and PTEN tumor suppressors.
In this study they demonstrated that overexpression of miR-138 represses BCR/ABL1 and CCND3
by binding to the coding and 37UTR regions, respectively .