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Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis

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Tumor Biology

Abstract

Paraoxonase (PON) enzymes possess antioxidant properties and protect against cardiovascular diseases. As a member of PON family, PON3 is primarily synthesized in the liver and poorly investigated. This study aimed to examine the expression of PON3 in human hepatocellular carcinoma (HCC) and investigate the clinical significance and biological function of PON3 in HCC patients. We first analyzed PON3 expression in 50 paired HCC samples (HCC tissues vs matched para-cancerous tissues) and 160 clinical HCC specimens by using immunohistochemistry (IHC). Our results showed that the expression of PON3 was downregulated in HCC and significantly associated with tumor-node-metastasis (TNM) stage, tumor size, and tumor number. Kaplan-Meier survival and Cox regression analyses showed that PON3 was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR). Finally, we aimed to reveal the biological function of PON3 in HCC growth and metastasis, and our results showed that overexpression of PON3 potently inhibited growth and metastasis of HCC. Collectively, our study demonstrated that PON3 exhibited tumor-suppressive effects toward HCC and it might serve as a novel prognostic marker in HCC.

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Acknowledgments

This study was supported by grants from Zhejiang Provincial Natural Science Foundation of China (nos. LY12H03006 and LY15H160058) and the National Natural Science Foundation of China (no. 81572291).

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Yuepeng Jin, Xiufen Zhao, Chunxiao Zheng & Yunfeng Shan

  2. Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Qiang Li & Yongyu Bai

  3. Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China

    Junjun Qiu & Shixu Lv

  4. Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Le-chi Ye

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  1. Yuepeng Jin
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Correspondence to Le-chi Ye.

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Supplementary Figure 1

Analysis for protein levels of PON3 in HCC cell lines. Protein levels of PON3 were determined by Western Blot in six HCC cell lines and one immortalized liver cell line. (JPG 159 kb)

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Jin, Y., Li, Q., Qiu, J. et al. Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis. Tumor Biol. 37, 14193–14203 (2016). https://doi.org/10.1007/s13277-016-5247-z

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  • DOI: https://doi.org/10.1007/s13277-016-5247-z

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