title: The role of peptidylarginine deiminase 4 in ovarian cancer cell tumorigenesis and invasion.
abstract: Peptidylarginine deiminase 4 (PADI4) is an enzyme that converts both histone arginine and mono-methyl arginine residues to citrulline, and it has been detected in various subtypes of ovarian cancer. However, the mechanism of action of PADI4 in ovarian carcinogenesis remains unknown. To examine the function of PADI4, we transfected two ovarian cancer cell lines, wild-type p53 A2780 and p53-null SKOV3, with PADI4-siRNA and negative control siRNA. The proliferation of both A2780 and SKOV3 cells decreased significantly following PADI4-siRNA treatment (P A2780 < 0.01; P SKOV3 < 0.001). The invasion and migration ability of A2780 cells also significantly decreased in response to PADI4-siRNA treatment (P < 0.001), but SKOV3 cells showed no such decrease. The apoptotic rate of A2780 cells increased in the presence of PADI4-siRNA, but there was no such increase in SKOV3 cells (P > 0.05). PCR arrays of A2780 cells treated with PADI4-siRNA revealed the up-regulated expression of six genes, including cell death-inducing DFFA-like effector a (CIDEA) and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and the down-regulation of seven genes, including integrin beta 3 (ITGB3) and BCL2-antagonist/killer 1 (BAK1). These results suggest an important role for PADI4 in the p53 pathway and the regulation of the proliferation, apoptosis, invasion and migration of ovarian cancer cells. Our study also demonstrated that PADI4 contributes to tumor metastasis by regulating the gene expression of insulin-like growth factor 1 (IGF1) and WAS/WASL-interacting protein family member 1 (WIPF1).
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, Shandong, China.|Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Cui
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Ya-Bing
authors.initials: YB
authors.lastname: Zheng
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Bing-Hui
authors.initials: BH
authors.lastname: Sun
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Lv
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China. fnrong@163.com.
authors.forename: Feng-Nian
authors.initials: FN
authors.lastname: Rong
authors.affiliation: Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated with Shandong University, Jinan, 250014, Shandong, China. chang-XT@163.com.
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006867:Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
chemical_list: D003598:Cytoskeletal Proteins; C583557:IGF1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C109903:WIPF1 protein, human; D007334:Insulin-Like Growth Factor I; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: Apoptosis; Cell proliferation; Invasion; Migration; Ovarian cancer; Peptidylarginine deiminase 4