title: Prp19 facilitates invasion of hepatocellular carcinoma via p38 mitogen-activated protein kinase/twist1 pathway.
abstract: Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. However, the pathological role of Prp19 in hepatocellular carcinoma (HCC) is still elusive. Here, we reported that Prp19 was increased in most HCC tissues and HCC cell lines, and its overexpression in HCC tissues was positively correlated with vascular invasion, tumor capsule breakthrough and poor prognosis. Prp19 potentiated migratory and invasive abilities of HCC cells in vitro and in vivo. Furthermore Prp19 facilitated Twist1-induced epithelial-mesenchymal transition. Mechanistic insights revealed that Prp19 directly binded with TGF-β-activated kinase1 (TAK1) and promoted the activation of p38 mitogen-activated protein kinase (MAPK), preventing Twist1 from degradation. Finally Prp19/p38 MAPK/Twist1 axis was attested in nude mice xenografts and HCC patient specimens. This work implies that the gain of Prp19 is a critical event during the progression of HCC, making it a promising target for malignancies with aberrant Prp19 expression.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ru-Yi
authors.initials: RY
authors.lastname: Xue
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.|Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Xi-Zhong
authors.initials: XZ
authors.lastname: Shen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D000072260:RNA Splicing Factors / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D048051:p38 Mitogen-Activated Protein Kinases; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human
keywords: liver cancer; signaling pathway; tumor progression; ubiquitination