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Overexpression of Protein Phosphatase 1γ (PP1γ) Is Associated with Enhanced Cell Proliferation and Poor Prognosis in Hepatocellular Carcinoma

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Abstract

Background

Protein phosphatase 1γ (PP1γ), as a member of the protein phosphatase 1 family, may be involved in regulation of multiple cellular processes, such as mitosis, cell survival, and apoptosis. However, little is known about the underlying mechanisms by which PP1γ regulates hepatocellular carcinoma development.

Aim

We investigated the expression profile of PP1γ in hepatocellular carcinoma (HCC) cell lines and human HCC specimens, as well as its potential prognostic significance in HCC.

Methods

PP1γ expression profile was detected in 94 HCC specimens using immunohistochemistry. PP1γ levels in HCC cells were downregulated by small interfering RNA (siRNA) transfection. Cell cycle progression and proliferation status of HCC cells and the effectiveness of doxorubicin were evaluated by flow cytometry and CCK-8 assay. The levels of PP1γ, CyclinD1, PCNA, Mdmx, p53, p21, and active caspase-3 were evaluated by Western blot analysis.

Results

PP1γ was upregulated in tumorous specimens, compared with adjacent nontumorous tissues. Univariate and multivariate survival analyses were conducted to determine the prognostic significance of PP1γ in HCC. The expression pattern of PP1γ was positively correlated with tumor size, histological grade, Ki-67 expression, and poor prognosis in HCC. In addition, depletion of PP1γ by siRNA could inhibit cell proliferation, resulted in G1 phase arrest, and attenuated resistance to doxorubicin in Huh7 cells.

Conclusions

PP1γ is upregulated in HCC cell lines and HCC specimens, promotes cancer cell proliferation through regulation of p53, and may be a potential target for treatment of HCC.

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Acknowledgement

This work was supported by the Science and Technology Project Foundation of Nantong (Nos. MS22015044, MS12015051).

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    Authors and Affiliations

    1. Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong, 226361, Jiangsu Province, China

      Chunsun Li, Guijuan Zong & Xudong Chen

    2. Department of Digestion, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, China

      Miaomiao Wu, Qingqing Liu & Cuihua Lu

    3. Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, China

      Chunhua Wan

    4. Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, China

      Huiling Zhou

    5. Department of Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, China

      Lu Hua

    6. Class 2 Grade 13, Clinical Medicine, Medical college, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, China

      Yuyan Chen

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    1. Chunsun Li
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    2. Miaomiao Wu
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    9. Xudong Chen
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    Correspondence to Xudong Chen or Cuihua Lu.

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    Chunsun Li and Miaomiao Wu contributed equally to this work.

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    Li, C., Wu, M., Zong, G. et al. Overexpression of Protein Phosphatase 1γ (PP1γ) Is Associated with Enhanced Cell Proliferation and Poor Prognosis in Hepatocellular Carcinoma. Dig Dis Sci 62, 133–142 (2017). https://doi.org/10.1007/s10620-016-4365-1

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    • DOI: https://doi.org/10.1007/s10620-016-4365-1

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