MiR-140-3p inhibits natural killer cytotoxicity to human ovarian cancer via targeting MAPK1

Journal of Biosciences volume 45, Article number: 66 (2020) Cite this article

Abstract

Natural killer (NK) cells have pivotal role in immunotherapy of human ovarian cancer (OC). Although microRNAs (miRNAs) participate in dysfunction of NK cells, how and whether miR-140-3p regulates cytotoxicity of NK cells in OC are uncertain. miR-140-3p and mitogen activated protein kinase 1 (MAPK1) abundances were examined via quantitative real-time polymerase chain reaction or western blot. Tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) abundances were examined via enzyme linked immunosorbent assay. NK cytotoxicity to OC was evaluated via lactate dehydrogenase release. The relevance of miR-140-3p and MAPK1 was proved via luciferase activity analysis. Murine xenograft experiment was applied to assess the function of miR-140-3p on NK cytotoxicity. miR-140-3p was elevated and MAPK1 was declined in NK cells from OC patients, while the levels were reversed after treatment of interleukin-2 (IL-2). MiR-140-3p addition mitigated IFN-γ and TNF-α production induced via IL-2 as well as NK-92 cytotoxicity to OC cells. Additionally, MAPK1 was negatively regulated via miR-140-3p and ablated the influence of miR-140-3p on cytotoxicity, cytokines levels. Besides, miR-140-3p enrichment facilitated tumor growth via suppressing function of NK cells in a xenograft model. miR-140-3p suppressed NK cytotoxicity to OC cells via mediating MAPK1, indicating a new avenue of ameliorating NK cells function for OC treatment.

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Acknowledgements

This research was supported via the Zhejiang Medical and Health Science and Technology Project (2020KY277), the Zhejiang Natural Science Foundation of China(Y18H040025)

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Affiliations

  1. Department of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo, 31500, Zhejiang, China

    Jiaying Wang, Miaohua Zhu, Xiaoming Zhou, Tingting Wang & Zhang Jing

  2. Department of Gynecology and Obstetrics, Yulin No.2 Hospital, Yulin, 719000, Shaanxi, China

    Yanni Xi

  3. Department of Immunology, The Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Wenjin Xi

Authors
  1. Jiaying Wang
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  2. Miaohua Zhu
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  3. Xiaoming Zhou
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  4. Tingting Wang
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  5. Yanni Xi
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  6. Zhang Jing
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  7. Wenjin Xi
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Correspondence to Zhang Jing or Wenjin Xi.

Additional information

Corresponding editor: BJ Rao.

Communicated by BJ RAO.

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Wang, J., Zhu, M., Zhou, X. et al. MiR-140-3p inhibits natural killer cytotoxicity to human ovarian cancer via targeting MAPK1. J Biosci 45, 66 (2020). https://doi.org/10.1007/s12038-020-00036-3

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Keywords

  • Ovarian cancer
  • natural killer cells
  • miR-140-3p
  • MAPK1
  • cytotoxicity