miR-20a inhibits the killing effect of natural killer cells to cervical cancer cells by downregulating RUNX1

• Published in: Biochemical and biophysical research communications 2018-10, Vol.505 (1), p.309-316
• Main Authors: Zhu, Suo-Yu, Wu, Qun-Ying, Zhang, Chen-Xia, Wang, Qiong, Ling, Jing, Huang, Xian-Ting, Sun, Xia, Yuan, Ming, Wu, Dan, Yin, Hua-Fang
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Cervical cancer; GENES; miR-20a; NATURAL KILLER CELLS; NEOPLASMS; PATIENTS; Runt-related transcription factor 1; TRANSCRIPTION FACTORS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.09.102

NK cells are presented in tumor microenvironments and acts as an essential defense line against multiple malignancies. Recently, miRNAs are reported to involve in the development of natural killer (NK) cells via negatively regulating gene expression. Here, we aim to explore the function and mechanism underlying how miR-20a modulated the killing effect of NK cells to cervical cancer cells. Abundances of miR-20a and runt-related transcription factor 1 (RUNX1) in NK cells from cervical cancer patients and healthy donors were detected by qRT-PCR and western blot. The releases of IFN-γ and TNF-α were determined by ELISA. The cytotoxicity of NK cells against cervical cancer cells was measured by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter, western blot, and RNA immunoprecipitation (RIP) assays were performed to assess the interaction between miR-20a and RUNX1. miR-20a was upregulated while RUNX1 was downregulated in NK cells from cervical cancer patients compared to healthy donors. IL-2 stimulated the releases of IFN-γ and TNF-α, and the killing effect of NK cells to cervical cancer cells, which was overturned by miR-20a introduction. RUNX1 was identified to be a target of miR-20a. Restoration of RUNX1 abolished the inhibitory effects of miR-20a on the secretions of IFN-γ and TNF-α, as well as the killing effect of NK cells to colorectal cancer cells. miR-20a attenuated the killing effect of NK cells to cervical cancer cells by directly targeting RUNX1. •MiR-20a was upregulated while RUNX1 was downregulated in NK cells from cervical cancer patients.•MiR-20a attenuated the natural killing effect of NK cells to cervical cancer cells.•RUNX1 was targeted by miR-20a.•MiR-20a inhibited the natural killing effect of NK cells to cervical cancer cells via targeting RUNX1.