RESUMO
BACKGROUND: 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. METHODS: 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. RESULT: 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. CONCLUSION: miR-20a attenuated the killing effect of NK cells to cervical cancer cells by directly targeting RUNX1.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Citotoxicidade Imunológica/genética , Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais/metabolismo , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Animais , Células Cultivadas , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Citotoxicidade Imunológica/imunologia , Regulação para Baixo , Feminino , Células HEK293 , Células HeLa , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante Heterólogo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismoRESUMO
The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.