PMID- 32385217 OWN - NLM STAT- MEDLINE DCOM- 20210331 LR - 20210331 IS - 0973-7138 (Electronic) IS - 0250-5991 (Linking) VI - 45 DP - 2020 TI - MiR-140-3p inhibits natural killer cytotoxicity to human ovarian cancer via targeting MAPK1. LID - 66 [pii] AB - 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-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) 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-gamma and TNF-alpha 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 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 via mediating MAPK1, indicating a new avenue of ameliorating NK cells function for OC treatment. FAU - Wang, Jiaying AU - Wang J AD - Department of Gynecology and Obstetrics, The affiliated Hospital of Medical School of Ningbo University, Ningbo 31500, Zhejiang, China. FAU - Zhu, Miaohua AU - Zhu M FAU - Zhou, Xiaoming AU - Zhou X FAU - Wang, Tingting AU - Wang T FAU - Xi, Yanni AU - Xi Y FAU - Jing, Zhang AU - Jing Z FAU - Xi, Wenjin AU - Xi W LA - eng PT - Journal Article PL - India TA - J Biosci JT - Journal of biosciences JID - 8100809 RN - 0 (Antagomirs) RN - 0 (IFNG protein, human) RN - 0 (Interleukin-2) RN - 0 (MicroRNAs) RN - 0 (Mirn140 microRNA, human) RN - 0 (Ribonucleotides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) SB - IM MH - Animals MH - Antagomirs/genetics/metabolism MH - Base Pairing MH - Base Sequence MH - Case-Control Studies MH - Cell Line, Tumor MH - Coculture Techniques MH - *Cytotoxicity, Immunologic MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Interferon-gamma/genetics/immunology MH - Interleukin-2/pharmacology MH - Killer Cells, Natural/*immunology/pathology MH - Mice MH - MicroRNAs/agonists/antagonists & inhibitors/*genetics/immunology MH - Mitogen-Activated Protein Kinase 1/*genetics/immunology MH - Ovarian Neoplasms/*genetics/immunology/pathology MH - Primary Cell Culture MH - Ribonucleotides/genetics/metabolism MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/genetics/immunology MH - Xenograft Model Antitumor Assays EDAT- 2020/05/10 06:00 MHDA- 2021/04/01 06:00 CRDT- 2020/05/10 06:00 PHST- 2020/05/10 06:00 [entrez] PHST- 2020/05/10 06:00 [pubmed] PHST- 2021/04/01 06:00 [medline] AID - 66 [pii] PST - ppublish SO - J Biosci. 2020;45:66.