Upregulation of the long non-coding rna hotair promotes esophageal squamous cell carcinoma metastasis and poor prognosis

Authors

  • Fang-Jun Chen,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Ming Sun,

    1. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Su-Qing Li,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Qing-Quan Wu,

    1. Huaian First Hospital, Nanjing Medical University, Huaian, Jiangsu, China
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  • Lv Ji,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Zhi-Li Liu,

    1. Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Guo-Zhi Zhou,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Gang Cao,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Lei Jin,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Hai-Wei Xie,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Chun-Mei Wang,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Jin Lv,

    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Wei De,

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
    • Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu Province, China.

      Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, China.

      Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210006, Jiangsu, China.

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  • Ming Wu,

    Corresponding author
    1. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
    • Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu Province, China.

      Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, China.

      Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210006, Jiangsu, China.

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  • Xiu-Feng Cao

    Corresponding author
    1. Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China
    • Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu Province, China.

      Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, China.

      Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210006, Jiangsu, China.

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  • Fang-Jun Chen, Ming Sun and Su-Qing Li contributed equally to this work and shoud be regarded as joint first authors.

Abstract

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers. © 2012 Wiley Periodicals, Inc.

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