title: Histone deacetylase 3 promotes pancreatic cancer cell proliferation, invasion and increases drug-resistance through histone modification of P27, P53 and Bax.
abstract: Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. In this study, our data showed that a higher level of HDAC3 protein expression was found in pancreatic cancer as compared to paired paracancerous tissues. Consistently, higher expression level of HDAC3 was found in all of the eight pancreatic cancer cell lines relative to human pancreatic ductal epithelial cells (HPDE). In addition, further function analysis revealed that HDAC3 can function as oncogenic protein, which could promote pancreatic cancer cell proliferation, migration and invasion, and may increase drug resistance. Moreover, the functional involvement of HDAC3 was partially correlated with post-induction repression of P53, P27 and Bax gene transcription, acting via H3K9 deacetylation. Taken together, our data suggest that HDAC3 participates in the pathogenesis and progression of pancreatic cancer through histone modification, which might be a pivotal epigenetic target against this devastating disease.
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Feng
authors: F
authors: Jiao
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Hai
authors: H
authors: Hu
authors: Department of Pathology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Cuncun
authors: C
authors: Yuan
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Ziliang
authors: Z
authors: Jin
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Zhen
authors: Z
authors: Guo
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Liwei
authors: L
authors: Wang
authors: Department of Oncology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, P.R. China.
authors: Lei
authors: L
authors: Wang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000093542:Gemcitabine; D000099186:Histone Deacetylase 3
chemical_list: D003841:Deoxycytidine; D006655:Histone Deacetylases; D006657:Histones; D046988:Proteasome Endopeptidase Complex; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000093542:Gemcitabine; D000099186:Histone Deacetylase 3; C494826:BAX protein, human; C114476:PSMD9 protein, human; C495901:TP53 protein, human