Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BCL6B is a potential tumor suppressor in human gastric cancer, but the regulation and mechanism of BCL6B in human hepatocellular carcinogenesis remain unclear. This study is to explore the epigenetic change and mechanism of BCL6B in human hepatocellular carcinoma (HCC). Nineteen hepatic cancer cell lines, 50 cases of adjacent tissue and 149 cases of HCC samples were employed. BCL6B is methylated in 100% (19/19) of human HCC cell lines, 40.0% (20/50) of adjacent tissue samples and 86.6% (129/149) of primary cancer samples. Methylation of BCL6B is associated with HBV positive (p < 0.05). But no association was found with age, sex, tumor size, differentiation, TNM stage, recurrence and survival. Loss of BCL6B expression was found in 19 of completely methylated HCC cell lines. BCL6B was re-expressed after 5-aza-2'-deoxycytidine treatment. Restoration of BCL6B expression suppressed cell proliferation, induced apoptosis and G1/S arrest in HCC cells. The expression of EGR1, a key component of p53 signaling, was increased after re-expression BCL6B in HCC cells. Re-expression of BCL6B activated p53 signaling and sensitized HCC cells to 5-fluorouracil. BCL6B is frequently methylated in human HCC and the expression of BCL6B is regulated by promoter region hypermethylation. BCL6B activates p53 signaling by increasing EGR1 expression in HCC.
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PMID:Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU. 2590 68

BCL6B, a homologue of BCL6, has been reported to be frequently methylated in human gastric cancer. The epigenetic change and the function of BCL6B remains to be elucidated in colorectal cancer. 7 colorectal cancer cell lines (RKO, HT-29, DLD1, LOVO, HCT116, SW480, SW620) and 102 cases of primary colorectal cancer samples were used in this study. Semi-quantitative RT-PCR, methylation specific PCR (MSP), Flow cytometry and western blot were employed. Loss of BCL6B expression was found in HT29, RKO LOVO, SW480, SW620 and DLD1 cells, and reduced expression was found in HCT116 cell line. Complete methylation was found in HT29, RKO, LOVO, SW480, SW620 and DLD1 cells, partial methylation was detected in HCT116 cells. Restoration of BCL6B expression was induced by 5-Aza treatment in these colorectal cancer cells. BCL6B was methylated in 79.4% (81/102) of primary human colorectal cancer and reduced expression was associated with promoter region hypermethylation (p < 0.05). Methylation of BCL6B is associated with late stage (p < 0.05) and lymph node metastasis (p < 0.05). Re-expression of BCL6B inhibited cell proliferation, invasion and migration in RKO and HT29 cells. BCL6B activated P53 signaling and induced apoptosis, Re-expression of BCL6B sensitized RKO and HT29 cells to 5-fluorouracil. In conclusion, BCL6B was frequently methylated in human colorectal cancer and its expression was regulated by promoter region methylation. Methylation of BCL6B is a prognostic and chemo-sensitive marker in colorectal cancer. BCL6B suppresses colorectal cancer growth by activating P53 signaling.
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PMID:Epigenetic silencing BCL6B induced colorectal cancer proliferation and metastasis by inhibiting P53 signaling. 2597 4

Zinc-finger and BTB/POZ domain-containing family proteins (ZBTB) are important transcription factors functioning as tumor suppressors or oncogenes, such as BCL6/ZBTB27 as a key oncoprotein for anti-cancer therapy. Through epigenome study, we identified ZBTB28/BCL6B/BAZF, a BTB/POZ domain protein highly homologous to BCL6, as a methylated target in multiple tumors. However, the functions and mechanism of ZBTB28 in carcinogenesis remain unclear. Methods: ZBTB28 expression and methylation were examined by reverse-transcription PCR and methylation-specific PCR. The effects and mechanisms of ectopic ZBTB28 expression on tumor cells were assessed with molecular biological and cellular approaches in vitro and in vivo. Results: Albeit broadly expressed in multiple normal tissues, ZBTB28 is frequently downregulated in aero- and digestive carcinoma cell lines and primary tumors, and correlated with its promoter CpG methylation status. Further gain-of-function study showed that ZBTB28 functions as a tumor suppressor inhibiting carcinoma cell growth in vitro and in vivo, through inducing cell cycle arrest and apoptosis of tumor cells. ZBTB28 suppresses cell migration and invasion by reversing EMT and cell stemness. ZBTB28 transactivates TP53 expression, through binding to the p53 promoter in competition with BCL6, while BCL6 itself was also found to be a direct target repressed by ZBTB28. Conclusion: Our results demonstrate that ZBTB28 functions as a tumor suppressor through competing with BCL6 for targeting p53 regulation. This newly identified ZBTB28/BCL6/p53 regulatory axis provides further molecular insight into carcinogenesis mechanisms and has implications in further improving BCL6-based anticancer therapy.
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PMID:Tumor suppressive BTB/POZ zinc-finger protein ZBTB28 inhibits oncogenic BCL6/ZBTB27 signaling to maintain p53 transcription in multiple carcinogenesis. 3175 89