Reduction of p53 gene expression in human primary hepatocellular carcinoma is associated with promoter region methylation without coding region mutation

2002 ◽  
Vol 176 (2) ◽  
pp. 169-174 ◽  
Author(s):  
I.P. Pogribny ◽  
S.Jill James
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Promoter Region ◽  
P53 Gene ◽  
Primary Hepatocellular Carcinoma ◽  
Coding Region

scholarly journals lncRNA MIR22HG-Derived miR-22-5p Enhances the Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Through the Inhibition of HDAC2 Activity

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiao Jin ◽  
Hao Hu ◽  
Siqi Yan ◽  
Long Jin ◽  
Yuliang Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Promoter Region ◽  
Animal Experiments ◽  
Primary Hepatocellular Carcinoma ◽  
Acetylation Level ◽  
Expression Levels

BackgroundWith the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.MethodA microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation in vitro. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2′-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the in vivo effect of MIR22HG on the radiosensitivity of hepatoma.ResultsIrradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity via miR-22-5p in HCC.ConclusionInhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.

scholarly journals DNA Methylation Silences Exogenous Gene Expression in Transgenic Birch Progeny

2020 ◽  
Vol 11 ◽  
Author(s):  
Minghao Ma ◽  
Xiaohui Chen ◽  
Yibo Yin ◽  
Ruixin Fan ◽  
Bo Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Promoter Region ◽  
Hybrid Progeny ◽  
Coding Region ◽  
Genetic Transmission ◽  
Expression Levels ◽  
Coding Regions ◽  
Exogenous Genes ◽  
Transgenic Progeny

The genetic stability of exogenous genes in the progeny of transgenic trees is extremely important in forest breeding; however, it remains largely unclear. We selected transgenic birch (Betula platyphylla) and its hybrid F1 progeny to investigate the expression stability and silencing mechanism of exogenous genes. We found that the exogenous genes of transgenic birch could be transmitted to their offspring through sexual reproduction. The exogenous genes were segregated during genetic transmission. The hybrid progeny of transgenic birch WT1×TP22 (184) and WT1×TP23 (212) showed higher Bgt expression and greater insect resistance than their parents. However, the hybrid progeny of transgenic birch TP23×TP49 (196) showed much lower Bgt expression, which was only 13.5% of the expression in its parents. To elucidate the mechanism underlying the variation in gene expression between the parents and progeny, we analyzed the methylation rates of Bgt in its promoter and coding regions. The hybrid progeny with normally expressed exogenous genes showed much lower methylation rates (0–29%) than the hybrid progeny with silenced exogenous genes (32.35–45.95%). These results suggest that transgene silencing in the progeny is mainly due to DNA methylation at cytosine residues. We further demonstrated that methylation in the promoter region, rather than in the coding region, leads to gene silencing. We also investigated the relative expression levels of three methyltransferase genes: BpCMT, BpDRM, and BpMET. The transgenic birch line 196 with a silenced Gus gene showed, respectively, 2.54, 9.92, and 4.54 times higher expression levels of BpCMT, BpDRM, and BpMET than its parents. These trends are consistent with and corroborate the high methylation levels of exogenous genes in the transgenic birch line 196. Therefore, our study suggests that DNA methylation in the promoter region leads to silencing of exogenous genes in transgenic progeny of birch.

scholarly journals DNMT1 inhibits hepatocellular carcinoma cells by altering the epigenetic modification of Marveld1 gene

2020 ◽  
Author(s):  
Song Yan Zhang ◽  
Qian Luo ◽  
Peng Wang ◽  
Hao Ran Zhao ◽  
Hai Tao Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Methylation Level ◽  
Promoter Region ◽  
Human Hepatoma ◽  
Rt Pcr ◽  
P16 Protein ◽  
Protein Expressions ◽  
Proliferation And Invasion

Abstract Objective To study the effect of DNA methyltransferase (DNMT1) on Marveld1 in hepatocellular Carcinoma (HCC), and explore its role in the molecular mechanism of HCC occurrence and development. Methods The expression level of Dnmt1 and Marveld1 genes was detected by RT-PCR in the intraoperative pathological specimens. The human hepatoma Bel7402 and SMMC7721 cell lines down-regulated by DNMT1 gene expression were constructed by SiRNA transfection. The methylation level of Marveld1 promoter region was detected after RT-PCR and West-blot verification. The expression of Marveld1 gene, cell proliferation, invasion and change of cell cycle were detected by RT-PCR and West-blot. The expressions of P53, CyclinD1, P21 and P16 protein were detected by West-blot method. Results The expression of DNMT1 gene in human hepatocarcinoma tissues was higher than that in adjacent tissues. The methylation level of the Marveld1 gene promoter region in human hepatoma cell line down-regulated by DNMT1 gene expression was decreased, the expression level of Marveld1 gene was increased, and the proliferation and invasion ability of cells were weakened. The cell cycle was showed as G1-S phase arrest; P53 and P16 protein expressions were up-regulated, and CyclinD1 and P21 protein expressions were down-regulated. Conclusions Dnmt1 gene is highly expressed in human hepatocarcinoma tissues. Down-regulation of DNMT1 gene expression can decrease the methylation level of Marveld1 promoter region, up-regulate Marveld1 gene and human P53 and P16 proteins expressions, and down-regulate CyclinD1 and P21 proteins expressions, inhibit the proliferation and invasion of human hepatoma cells and can cause cell cycle G1-S arrest.

scholarly journals DNMT1 inhibits hepatocellular carcinoma cells by altering the epigenetic modification of Marveld1 gene

2020 ◽  
Author(s):  
Song Yan Zhang ◽  
Qian Luo ◽  
Peng Wang ◽  
Hao Ran Zhao ◽  
Hai Tao Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Methylation Level ◽  
Promoter Region ◽  
Human Hepatoma ◽  
Rt Pcr ◽  
P16 Protein ◽  
Protein Expressions ◽  
Proliferation And Invasion

Abstract Objective to study the effect of DNA methyltransferase (DNMT1) on Marveld1 in hepatocellular Carcinoma (HCC), and explore its role in the molecular mechanism of HCC occurrence and development.Methods The expression level of Dnmt1 and Marveld1 genes was detected by RT-PCR in the intraoperative pathological specimens. The human hepatoma Bel7402 and SMMC7721 cell lines down-regulated by DNMT1 gene expression were constructed by SiRNA transfection. The methylation level of Marveld1 promoter region was detected after RT-PCR and West-blot verification. The expression of Marveld1 gene, cell proliferation, invasion and change of cell cycle were detected by RT-PCR and West-blot. The expressions of P53, CyclinD1, P21 and P16 protein were detected by West-blot method.Results The expression of DNMT1 gene in human hepatocarcinoma tissues was higher than that in adjacent tissues. The methylation level of the Marveld1 gene promoter region in human hepatoma cell line down-regulated by DNMT1 gene expression was decreased, the expression level of Marveld1 gene was increased, and the proliferation and invasion ability of cells were weakened. The cell cycle was showed as G1-S phase arrest; P53 and P16 protein expressions were up-regulated, and CyclinD1 and P21 protein expressions were down-regulated.Conclusions Dnmt1 gene is highly expressed in human hepatocarcinoma tissues. Down-regulation of DNMT1 gene expression can decrease the methylation level of Marveld1 promoter region, up-regulate Marveld1 gene and human P53 and P16 proteins expressions, and down-regulate CyclinD1 and P21 proteins expressions, inhibit the proliferation and invasion of human hepatoma cells and can cause cell cycle G1-S arrest.

scholarly journals DNMT1 inhibits hepatocellular carcinoma cells by altering the epigenetic modification of Marveld1 gene

2020 ◽  
Author(s):  
Song-Yan Zhang ◽  
Qian Luo ◽  
Peng Wang ◽  
Hao-Ran Zhao ◽  
Hai-Tao Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Methylation Level ◽  
Promoter Region ◽  
Human Hepatoma ◽  
Rt Pcr ◽  
P16 Protein ◽  
Protein Expressions ◽  
Proliferation And Invasion

Abstract Background To study the effect of DNA methyltransferase (DNMT1) on Marveld1 in hepatocellular Carcinoma (HCC), and explore its role in the molecular mechanism of HCC occurrence and development. Methods The expression levels of Dnmt1 and Marveld1 genes were detected by RT-PCR in the intraoperative pathological specimens. The human hepatoma Bel7402 and SMMC7721 cell lines down-regulated by DNMT1 gene expression were constructed by SiRNA transfection. The methylation level of Marveld1 promoter region was detected after RT-PCR and West-blot verification. The expression of Marveld1 gene, cell proliferation, invasion and change of cell cycle were detected by RT-PCR and West-blot. The expressions of P53, CyclinD1, and P21 and P16 protein were detected by West-blot method. Results The expression of DNMT1 gene in human hepatocarcinoma tissues was higher than that in adjacent tissues. The methylation level of the Marveld1 gene promoter region in human hepatoma cell line down-regulated by DNMT1 gene expression was decreased, the expression level of Marveld1 gene was increased, and the proliferation and invasion ability of cells were weakened. The cell cycle was showed as G1-S phase arrest; P53 and P16 protein expressions were up-regulated, and CyclinD1 and P21 protein expressions were down-regulated. Conclusions Dnmt1 gene is highly expressed in human hepatocarcinoma tissues. Down-regulation of DNMT1 gene expression can decrease the methylation level of Marveld1 promoter region, up-regulate Marveld1 gene and human P53 and P16 proteins expressions, and down-regulate CyclinD1 and P21 proteins expressions, inhibit the proliferation and invasion of human hepatoma cells and can cause cell cycle G1-S arrest.

Sign in / Sign up

Export Citation Format

Share Document