title: Paraoxonase 3 inhibits cell proliferation and serves as a prognostic predictor in hepatocellular carcinoma.
abstract: Paraoxonase 3 (PON3) exerts prominent anti-inflammation and anti-oxidation properties mainly at the cellular level, and is primarily expressed in the liver. However, its role in HCC remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of PON3 in HCC. PON3 mRNA and protein levels were respectively determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) of tissue microarray. We found that PON3 was downregulated in most HCCs. Kaplan-Meier and log-rank test showed that PON3 downregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in all HCC patients, especially early-stage HCC patients. Cox regression analysis revealed that the PON3 downregulation was an independent risk factor for RFS and OS. Gain- and loss-of-function experiments revealed that PON3 suppressed cell proliferation in vivo and in vitro, which was attributed to its cell-cycle arrest effect. In addition, microarray analysis showed that some pro-proliferative genes were elevated when PON3 was knockdown, and these genes possibly involved in the underlying mechanisms. In conclusion, our studies reveal the cell proliferation inhibitory function of PON3 and offer a potential prognostic predictor and therapeutic target for HCC.
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Sheng-Xian
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi-Fei
authors.initials: QF
authors.lastname: Tao
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Xu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhen-Guang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Kong-Ying
authors.initials: KY
authors.lastname: Lin
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zong-Yan
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Jin-Zhao
authors.initials: JZ
authors.lastname: Ma
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Chuan-Chuan
authors.initials: CC
authors.lastname: Zhou
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D043303:Aryldialkylphosphatase; C113656:PON3 protein, human
keywords: cDNA microarray; cell proliferation; hepatocellular carcinoma; paraoxonase 3; prognostic predictor