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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This research was supported via the Zhejiang Medical and Health Science and Technology Project (2020KY277), the Zhejiang Natural Science Foundation of China(Y18H040025)
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
- Ovarian cancer
- natural killer cells