The effects of ribavirin on the viability and clonogenicity of the B‑cell lymphoma cell line Pfeiffer (EZH2‑mutant), Toledo (EZH2 wild‑type) and cutaneous T‑cell lymphoma Hut78 cell line were assessed.
Consistent with this observation, TCEAL7-downregulated clones showed higher levels of NF-kappaB targets, such as pro-proliferative (cyclin-D1 and cMyc), pro-angiogenic (interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF)), inflammatory (intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase-2 (Cox-2)) and anti-apoptotic (B-cell lymphoma-extra large (Bcl-xl)) genes when compared with vector controls.
The DEGs were as follows: Phosphatidylinositol‑dependent kinase 1 (PDK1), a key gene upstream of protein kinase B (AKT); angiopoietin 2, a B‑cell lymphoma 2 (Bcl‑2)‑inhibited gene; transcription factor 4, glutathione S‑transferase P91 and ubiquitin‑specific protease 33, mitogen‑activated protein kinase (MAPK)‑related genes; oxidative stress induced growth inhibitor 1, related to the P53 pathway; Bcl‑2, P53, ERK (MAPK1/3), c‑Jun N‑terminal kinase (MAPK8/9), and P38 (MAPK14), all of which are key genes involved in the AKT signaling pathway.
These findings represent a novel promising approach for silencing MYC-miRNA-EZH2 amplification loop for combinatorial therapy of aggressive B-cell lymphomas.
We discuss our current understanding of EZH2 somatic mutations frequently found in B-cell lymphomas and recurrent mutations in various other epigenetic regulators as novel molecular predictors and determinants of PRC2 sensitivity.
Tumor protein 53 (TP53), a transcriptional factor, induces expression of the B-cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter but inhibits B-cell lymphoma 2 (BCL2) promoter-driven transcription through a responsive region in the BCL2 promoter.
Also, LA cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and cyclooxygenase-2 (COX-2) in two HCC cells.
The mRNA expression levels of the apoptosis‑related genes caspase-3 (CASP3) and B‑cell lymphoma‑2‑associated X protein (BAX), and of the potential target genes for miR‑181a, c‑MET, cyclooxygenase 2 (COX‑2) and snail family transcriptional repressor 2 (SNAI2) were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR).
Further research indicated that DSS‑ and cellular tumor antigen p53 (p53)‑alone or combination treatment was able to decrease the expression levels of apoptosis regulator BAX and caspase‑3, and increase the expression of apoptosis regulator B‑cell lymphoma (Bcl)‑2 in ALD‑stimulated cardiomyocytes.
Compared with those in the control group, the apoptosis rate of T24 cells was remarkably increased after treatment with different doses of puerarin or EX527, and the expression level of apoptosis-related protein Bcl-2-associated X protein (Bax) was also significantly increased, but the expression level of B-cell lymphoma 2 (Bcl-2) was decreased, and both the protein and mRNA expression levels of SIRT1 and p53 also significantly declined.
Here, we show that deregulated expression of AID causes widespread genome instability, which alone is insufficient to induce B cell lymphoma; transformation requires concomitant loss of the tumor suppressor p53.
The aim of the present study was to investigate the role of B-cell lymphoma 2 (Bcl-2) and tumor protein p53 (p53) in the proliferation and apoptosis of hemangioma cells.
Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals.
Mechanistically, the apoptosis-related protein, B-cell lymphoma-2 (Bcl-2), was downregulated in KIFC1 small interfering RNA-treated groups, whereas thee levels of Bcl-2-associated X protein and p53 were upregulated.
The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000).
The study further demonstrated that combined treatment significantly decreased HEC apoptosis through the upregulation of B-cell lymphoma 2 (Bcl-2) and P53 expression levels, as well as downregulation of Bcl-2-associated X protein and caspase-3 levels.
Twelve (46%) of 26 lymphoblastic B-cell lymphomas exhibited changes in the p19(Arf)-Mdm2-p53 tumor suppressor axis, an important pathway for Myc-dependent apoptosis.
Alteration to down-stream signaling of p53 including activation of pro-apoptosis protein (Bcl-2-associated X protein; Bax), reduction of anti-apoptosis (B cell lymphoma 2; Bcl-2 and myeloid cell leukemia 1; Mcl-1) and suppression on protein kinase B (Akt) survival pathway were notified in TDB-treated lung cancer cells.