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Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer

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Tumor Biology

Abstract

Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), an enhancer of zeste homolog 2 (EZH2), IRAIN reduced PC tumor cell apoptosis and induced growth arrest by silencing the expression of Kruppel-like factor 2 (KLF2) and P15. Moreover, IRAIN expression was inversely correlated with that of KLF2 and P15 in PC tissues. To our knowledge, this is the first report elucidating the role and mechanism of IRAIN in PC progression.

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Acknowledgments

This work was supported by the Six Talents Peak Project of Jiangsu Province (WSN-050), the Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (YKK13178), and the Medical Science and Technology Development Foundation, Nanjing Medical University (2014NJMUZD074).

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Authors and Affiliations

  1. Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People’s Republic of China

    Yifan Lian, Juan Wang, Jie Ding, Zhonghua Ma, Juan Li & Keming Wang

  2. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, People’s Republic of China

    Jing Feng

  3. Department of Oncology, The Second Hospital of Nanjing, Nanjing, 210000, Jiangsu, People’s Republic of China

    Peng Peng

  4. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210000, Jiangsu, People’s Republic of China

    Wei De

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  1. Yifan Lian
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  2. Juan Wang
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  3. Jing Feng
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  4. Jie Ding
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  5. Zhonghua Ma
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  6. Juan Li
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  7. Peng Peng
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  8. Wei De
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  9. Keming Wang
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Corresponding author

Correspondence to Keming Wang.

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Informed consent was obtained from all patients. Our study was approved by the Research Ethics Committee of Nanjing Medical University, China.

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Additional information

Yifan Lian, Juan Wang, and Jing Feng contributed equally to the work.

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Lian, Y., Wang, J., Feng, J. et al. Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer. Tumor Biol. 37, 14929–14937 (2016). https://doi.org/10.1007/s13277-016-5380-8

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  • DOI: https://doi.org/10.1007/s13277-016-5380-8

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