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Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma

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Abstract

Background

Cell division cycle 5-like (Cdc5L), as a pre-mRNA splicing factor, is a regulator of mitotic progression. Previous study found that deletion of endogenous Cdc5L decreases the cell viability via dramatic mitotic arrest, while the role of Cdc5L in cancer biology remains under debate.

Aims

To investigate the involvement of Cdc5L in the progression of hepatocellular carcinoma (HCC).

Methods

In this study, the expression of Cdc5L was evaluated by Western blot in 8 paired fresh HCC tissues and immunohistochemistry on 116 paraffin-embedded slices. We treated HCC cells by nocodazole to analyze the role of Cdc5L in mitotic progress. To determine whether Cdc5L could regulate the proliferation of HCC cells, we increased endogenous Cdc5L and analyzed the proliferation of HCC cells using Western blot, CCK8, flow cytometry assays, and colony formation analyses. Furthermore, Cdc5L-siRNA oligos were used to confirm that Cdc5L plays an essential role in HCC development.

Results

Cdc5L was highly expressed in HCC and significantly associated with multiple clinicopathological factors, including AJCC stage, tumor size, and Ki-67. Besides, univariate and multivariate survival analyses demonstrated that high Cdc5L expression was an independent prognostic factor for HCC patients’ poor survival. Overexpression of Cdc5L favors cell cycle progress of HCC cells, while downregulation of Cdc5L results in cell cycle arrest at G2/M phase and reduced cell proliferation of HCC cells.

Conclusions

Our findings suggested that Cdc5L could play an important role in the tumorigenesis of HCC and thus be a potential therapeutical target to prevent HCC progression.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 81472272) and Natural Youth Foundation of China (No. 81401985).

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    Authors and Affiliations

    1. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Huiyuan Qiu, Wenkai Ni & Runzhou Ni

    2. Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Xiubing Zhang, Weidong Shi, Hui Fan, Jian Xu & Yongmei Chen

    3. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Tao Tao

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    1. Huiyuan Qiu
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    Correspondence to Runzhou Ni or Tao Tao.

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    Huiyuan Qiu and Xiubing Zhang have contributed equally to this work.

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    Qiu, H., Zhang, X., Ni, W. et al. Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma. Dig Dis Sci 61, 795–805 (2016). https://doi.org/10.1007/s10620-015-3937-9

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    • DOI: https://doi.org/10.1007/s10620-015-3937-9

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