title: Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53-dependent manner.
abstract: Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer-related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT-PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK-8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA-mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual-luciferase reporter assay and ChIP-qPCR analysis. PRC1 was up-regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease-specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell-cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kang
authors.affiliation: Department of General Surgery, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Centre for Experimental Animal, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Laboratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Medical School, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D010881:Piperidones
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004148:Dioxolanes; D016159:Tumor Suppressor Protein p53; C116662:PRC1 protein, human; C495901:TP53 protein, human; C498077:piperlongumine; D010881:Piperidones
keywords: PRC1; gastric cancer; oncogene; p53; piperlongumine