Paraoxonase 3 inhibits cell proliferation and serves as a prognostic predictor in hepatocellular carcinoma
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Jie Cai1,*, Sheng-Xian Yuan1,*, Fu Yang2,*, Qi-Fei Tao1,*, Yuan Yang1, Qing-Guo Xu1, Zhen-Guang Wang1, Jian Yu1, Kong-Ying Lin1, Zong-Yan Wang1, Jin-Zhao Ma2, Chuan-Chuan Zhou2, Fang Wang2, Shu-Han Sun2, Wei-Ping Zhou1
1The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
2The Department of Medical Genetics, Second Military Medical University, Shanghai, China
*These authors contributed equally to this work
Wei-Ping Zhou, email: firstname.lastname@example.org
Shu-Han Sun, email: email@example.com
Keywords: paraoxonase 3, hepatocellular carcinoma, prognostic predictor, cell proliferation, cDNA microarray
Received: February 26, 2016 Accepted: September 02, 2016 Published: September 20, 2016
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.
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