Wang, JiayingZhu, MiaohuaZhou, XiaomingWang, TingtingXi, YanniJing, ZhangXi, Wenjin2020-11-182020-11-182020-05Wang Jiaying, Zhu Miaohua, Zhou Xiaoming, Wang Tingting, Xi Yanni, Jing Zhang, Xi Wenjin. MiR-140-3p inhibits natural killer cytotoxicity to human ovarian cancer via targeting MAPK1. Journal of Biosciences. 2020 May; : 1-100250-59910973-7138http://imsear.searo.who.int/handle/123456789/214296Natural killer (NK) cells have pivotal role in immunotherapy of human ovarian cancer (OC). AlthoughmicroRNAs (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. Tumornecrosis factor-a (TNF-a) and interferon-c (IFN-c) abundances were examined via enzyme linkedimmunosorbent assay. NK cytotoxicity to OC was evaluated via lactate dehydrogenase release. The relevanceof miR-140-3p and MAPK1 was proved via luciferase activity analysis. Murine xenograft experiment wasapplied to assess the function of miR-140-3p on NK cytotoxicity. miR-140-3p was elevated and MAPK1 wasdeclined in NK cells from OC patients, while the levels were reversed after treatment of interleukin-2 (IL-2).MiR-140-3p addition mitigated IFN-c and TNF-a production induced via IL-2 as well as NK-92 cytotoxicityto OC cells. Additionally, MAPK1 was negatively regulated via miR-140-3p and ablated the influence of miR140-3p 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 viamediating MAPK1, indicating a new avenue of ameliorating NK cells function for OC treatment.Ovarian cancernatural killer cellsmiR-140-3pMAPK1cytotoxicityJournal ArticleIndiaDepartment of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, ChinaDepartment of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, ChinaDepartment of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, ChinaDepartment of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, ChinaDepartment of Gynecology and Obstetrics, Yulin No.2 Hospital, Yulin 719000, Shaanxi, ChinaDepartment of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, ChinaDepartment of Immunology, The Fourth Military Medical University, Xi’an 710032, Shaanxi, China