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The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1

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Tumor Biology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is seriously resistant to radiotherapy and the mechanism is largely unknown. HOX transcript antisense intergenic RNA (HOTAIR) is overexpressed in PDAC. However, the function of HOTAIR has never been related to the radiosensitivity of PDAC. In this present study, the expression of HOTAIR in the PDAC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and the association between HOTAIR expression levels and X-ray treatment in PDAC cell lines was investigated. Additionally, the influence of HOTAIR knockdown on radiosensitivity, proliferation, and apoptosis of PDAC cells after radiation was evaluated by colony formation assays, Cell Counting Kit-8 (CCK-8) assays, and flow cytometry, respectively. Furthermore, the correlation between HOTAIR and Wnt inhibitory factor 1 (WIF-1) expression in PDAC cell lines and tissues was studied to assess the role of HOTAIR and WIF-1 in the radiosensitivity of PDAC. The results confirmed that HOTAIR expression was significantly increased in the PDAC cell lines and tissues (n = 90) compared with human normal pancreatic ductal epithelial cell line (HPDE) and matched adjacent normal tissues (n = 90). Functionally, HOTAIR knockdown enhanced the radiosensitivity of PDAC cells, reduced the proliferation, and increased the apoptosis of cells after radiation. And HOTAIR silencing increased the expression of WIF-1. Furthermore, the overexpression of WIF-1 revealed that HOTAIR modulated the radiosensitivity of PDAC cells by regulating the expression of WIF-1. These data reveals that HOTAIR can affect the radiosensitivity of PDAC cells partly via regulating the expression of WIF-1, and HOTAIR-WIF-1 axis is a potential target for PDAC radiotherapy.

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Authors’ contributions

YML and RFC designed the experiments and analyzed the raw data. YHJ and ZHL performed the experiments, disposed and analyzed the data, and wrote this manuscript. SYZ, HMC, XHZ, WCG, ZFB, KYY, YXW, WZL, and LTL were involved in the experiments and analysis of data. All the authors have read and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Yanhui Jiang, Xiaohui Zhao, Zhuofei Bi, Kaiyun You, Liting Li & Yimin Liu

    2. Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Zhihua Li, Huimou Chen & Wenzhu Li

    3. Department of Pancreaticobiliary Surgery, Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Shangyou Zheng, Wenchao Gao, Yingxue Wang & Rufu Chen

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    1. Yanhui Jiang
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    Yanhui Jiang and Zhihua Li contributed equally to this work.

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    Jiang, Y., Li, Z., Zheng, S. et al. The long non-coding RNA HOTAIR affects the radiosensitivity of pancreatic ductal adenocarcinoma by regulating the expression of Wnt inhibitory factor 1. Tumor Biol. 37, 3957–3967 (2016). https://doi.org/10.1007/s13277-015-4234-0

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