Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer

GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 an...

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Veröffentlicht in:PloS one 2011-11, Vol.6 (11), p.e27684
Hauptverfasser: He, ShanShan, Wang, Feng, Yang, LiJuan, Guo, ChuanYong, Wan, Rong, Ke, AiWu, Xu, Ling, Hu, GuoYong, Xu, XuanFu, Shen, Jie, Wang, XingPeng
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Sprache:eng
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Zusammenfassung:GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs. Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered. IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027684