Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma

Authors

  • Zheng-Jun Zhou,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Sciences, Fudan University, Shanghai, China
    3. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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    • Z.-J.Z., Z.D. and S.-L.Z. contributed equally to this work.

  • Zhi Dai,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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    • Z.-J.Z., Z.D. and S.-L.Z. contributed equally to this work.

  • Shao-Lai Zhou,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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    • Z.-J.Z., Z.D. and S.-L.Z. contributed equally to this work.

  • Xiu-Tao Fu,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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  • Yi-Ming Zhao,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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  • Ying-Hong Shi,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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  • Jian Zhou,

    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Sciences, Fudan University, Shanghai, China
    3. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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  • Jia Fan

    Corresponding author
    1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Sciences, Fudan University, Shanghai, China
    3. Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
    • Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China
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    • Tel.: +86-21-6404-1990, Fax: +86-21-6403-7181


Abstract

Heterogeneous ribonucleoprotein (hnRNP) A1 is a member of the A/B subfamily of ubiquitously expressed hnRNPs, which have a wide variety of functions in gene expression and signal transduction. To investigate the biological function and clinical significance of hnRNP A1 in hepatocellular carcinoma (HCC), we measured hnRNP A1 expression in four HCC cell lines and two independent cohorts of HCC patients. We found that hnRNP A1 was overexpressed in the highly metastatic HCC cell lines and in tumor tissues of patients with recurrent HCC. Knockdown of hnRNP A1 in highly metastatic HCC cells caused a significant decrease in cell invasion, while upregulation of hnRNP A1 in poorly metastatic HCC cells led to a significant increase in their invasive capacity. We found that this effect may occur through the regulation of CD44v6 expression by hnRNP A1 in HCC cells. Both quantitative reverse transcription-polymerase chain reaction (qRT-RCR) and immunohistochemistry revealed that hnRNP A1 was upregulated in HCC tissues and coincided with overexpression of CD44v6. HCC patients with high hnRNP A1 tended to have higher levels of CD44v6, shorter overall survival (OS) and higher rates of tumor recurrence. Multivariate analyses revealed that hnRNP A1 alone or in combination with CD44v6 were independent prognostic indicators for OS and time to recurrence and have potential as therapeutic targets. In conclusion, overexpression of hnRNP A1 promotes HCC invasion by regulating the level of CD44v6 and indicates a poor prognosis for HCC patients after curative resection.

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