title: Down-regulation of DNA methyltransferase 3B in staurosporine-induced apoptosis and its mechanism in human hepatocarcinoma cell lines.
abstract: Abnormal DNA methylation is one of the important characteristics in tumor cells. Apoptosis plays an essential role in cell survival and processing. It is not clear whether DNA methyltransferases (DNMTs) change in apoptosis and how DNMTs are regulated in apoptosis. In this study, we found that SMMC-7721 or BEL-7404 cells were induced to apoptosis by STS, meanwhile the DNMT3B protein and mRNA level were decreased. To explore the mechanism of DNMT3B down-regulation, we found that the mRNA decay was not changed and core promoter activity of DNMT3B gene was decreased in STS-induced apoptosis. In order to figure out the signal molecule involved in transcriptional regulation of DNMT3B gene by STS, p-JNK, p-ERK, and p-p38 were examined. In STS-induced apoptosis p-JNK level was increased, and p-ERK and p-p38 were decreased. Furthermore, the inhibitor of p-JNK significantly alleviated the decline of DNMT3B protein. We also found that the siRNA of DNMT3B strengthened the cleavage of PARP and pro-caspase-3 as well as up-regulated the p16 gene expression in STS-treated cells. We concluded here that STS-regulated DNMT3B gene expression via p-JNK and down-regulation of DNMT3B-mediated STS-induced apoptosis through the up-regulation p16 expression.
authors: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Chao
authors: C
authors: Zhao
authors: Peng
authors: P
authors: Yin
authors: Chuanzhong
authors: C
authors: Mei
authors: Na
authors: N
authors: Li
authors: Wantong
authors: W
authors: Yao
authors: Xin
authors: X
authors: Li
authors: Jingjing
authors: J
authors: Qi
authors: Kun
authors: K
authors: Fan
authors: Zengxia
authors: Z
authors: Li
authors: Liying
authors: L
authors: Wang
authors: Yinghong
authors: Y
authors: Shi
authors: Shuangjian
authors: S
authors: Qiu
authors: Jia
authors: J
authors: Fan
authors: Xiliang
authors: X
authors: Zha
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019942:Genes, p16; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D034741:RNA, Small Interfering; D019311:Staurosporine / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D004791:Enzyme Inhibitors; D048670:MAP Kinase Kinase 4; D034741:RNA, Small Interfering; D019311:Staurosporine; D048051:p38 Mitogen-Activated Protein Kinases; D000097584:DNA Methyltransferase 3B
references: Cancer Res. 2003 Oct 1;63(19):6110-5
references: 14559786
references: Cancer Sci. 2010 Jun;101(6):1431-9
references: 20398055
references: Cancer Cell. 2008 Aug 12;14(2):156-65
references: 18691550
references: J Clin Invest. 2010 Feb;120(2):521-32
references: 20093774
references: Cell. 1999 Oct 29;99(3):247-57
references: 10555141
references: Cell. 2007 Feb 23;128(4):683-92
references: 17320506
references: Cancer Res. 1995 Oct 15;55(20):4525-30
references: 7553621
references: Nat Rev Cancer. 2009 Aug;9(8):537-49
references: 19629069
references: Cancer Res. 1999 Feb 15;59(4):793-7
references: 10029064
references: Cancer Res. 1997 Aug 15;57(16):3347-50
references: 9269993
references: J Biol Chem. 2006 Mar 10;281(10):6760-7
references: 16407188
references: Oncogene. 2003 Mar 27;22(12):1866-71
references: 12660822
references: Gene. 1999 Aug 5;236(1):87-95
references: 10433969
references: Science. 2000 May 5;288(5467):870-4
references: 10797012
references: Protein Cell. 2010 Mar;1(3):218-26
references: 21203968
references: J Biol Chem. 2010 Feb 26;285(9):6259-64
references: 20028971
references: Neuroscience. 2011 Oct 27;194:272-81
references: 21843603
references: J Neurochem. 2000 Apr;74(4):1621-6
references: 10737620
references: Mol Cell. 2006 Mar 3;21(5):701-10
references: 16507367
references: Science. 1995 Mar 10;267(5203):1456-62
references: 7878464
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: Br J Cancer. 1972 Aug;26(4):239-57
references: 4561027
references: Cell. 2006 Feb 10;124(3):601-13
references: 16469705
references: Cell Signal. 2007 Nov;19(11):2255-63
references: 17716861
references: J Cell Biochem. 2010 Sep 1;111(1):158-67
references: 20506537
references: Int J Oncol. 2005 Jun;26(6):1575-80
references: 15870872
references: J Antibiot (Tokyo). 1977 Apr;30(4):275-82
references: 863788
references: Cancer Res. 1995 Oct 15;55(20):4531-5
references: 7553622
references: J Clin Oncol. 1998 Mar;16(3):1197-206
references: 9508208
references: Hum Genet. 1989 Sep;83(2):155-8
references: 2550354
references: Genes Dev. 2004 Dec 1;18(23):2905-15
references: 15545623
references: J Biol Chem. 2002 Aug 2;277(31):28176-81
references: 12015329
references: Anticancer Res. 2011 Sep;31(9):2723-32
references: 21868513
references: Clin Cancer Res. 2004 Nov 15;10(22):7484-9
references: 15569978
references: Genes Dev. 2002 Jan 1;16(1):6-21
references: 11782440
references: Carcinogenesis. 2011 Feb;32(2):224-32
references: 20980350
references: Mol Cell Biol. 2002 Jul;22(13):4929-42
references: 12052897