ABSTRACT
BACKGROUND: The intricate interplay between the immune system and tumor plays a pivotal role in thyroid cancer (TC) pathogenesis, potentially influencing both the causation and therapeutic outcomes. Despite extensive research, existing literature offers ambiguous insights regarding the association between immune cell traits and thyroid cancer progression. METHODS: To elucidate the potential causal relationships, we conducted an integrated two-sample Mendelian randomization (MR) analysis. This study utilized publicly genetic datasets to explore the causalities between 731 immune cell traits (categorized into four trait types across seven panels) and thyroid cancer. We ensured the robustness of our findings through comprehensive sensitivity analyses, meticulously assessing potential sources of bias such as pleiotropy. RESULTS: After False Discovery Rate (FDR) correction, six immune cell traits were identified to be significantly associated with thyroid cancer risk (Inverse Variance Weighted, IVW): Absolute count of gamma delta T cells/ T-cell receptor gamma delta absolute count (TCRgd AC) 0.8464 (OR95% CI = 0.7477-0.9580, P = 0.0083, PFDR = 0.0103); CD8 on bright CD8 cells (CD8 on CD8br) 0.8867 (OR95% CI = 0.8159-0.9637, P = 0.0047, PFDR = 0.0093); CD127 on CD45RA negative CD4 T cells not regulatory T cells (CD127 on CD45RA- CD4 not Treg) 0.8969 (OR95% CI = 0.8192-0.9820, P = 0.0186, PFDR = 0.0186); CD80 on CD62L positive plasmacytoid dendritic cells (CD80 on CD62L+ plasmacytoid DC) 1.1091 (OR95% CI = 1.0267-1.1982, P = 0.0086, PFDR = 0.0103); CD80 on plasmacytoid DC 1.1283 (OR95% CI = 1.0462-1.2168, P = 0.0017, PFDR = 0.0093); Side scatter-area on bright CD8 cells (SSC - A on CD8br) 1.1622 (OR95% CI = 1.0507-1.2854, P = 0.0035, PFDR = 0.0093). CONCLUSIONS: Our study demonstrated the causalities between immune cell traits and thyroid cancers by Mendelian randomization study, thus guiding future mechanism studies.
ABSTRACT
In this study, we investigated the impact of microRNA-34a (miR-34a) on lower limb arteriosclerosis obliterans in rats through the Sirtuin 1 (Sirt1) signaling pathway. Thirty-six Sprague-Dawley rats were divided into normal, model, and miR-34a mimics groups. Rats in the normal group were raised normally, while the model group underwent lower limb arteriosclerosis obliterans induction and received saline injections. The miR-34a mimics group also underwent arteriosclerosis obliterans modeling but received miR-34a mimics injections. Immunohistochemistry revealed significantly increased vascular endothelial growth factor (VEGF) expression in both model and miR-34a mimics groups compared to the normal group, with the miR-34a mimics group showing higher levels. Western blotting indicated elevated Sirt1 protein expression in both non-normal groups, with the miR-34a mimics group exhibiting significantly higher levels. Quantitative polymerase chain reaction (qPCR) demonstrated higher levels of miR-34a, VEGF mRNA, and Sirt1 mRNA in the model group compared to the normal group, but significantly lower levels than the miR-34a mimics group. Enzyme-linked immunosorbent assay (ELISA) showed increased VEGF content in the model group compared to the normal group but decreased compared to the miR-34a mimics group. Hemorrheological detection revealed a reduced PU index in both non-normal groups compared to the normal group, with a significant increase in the miR-34a mimics group compared to the model group. Overall, miR-34a upregulation enhanced VEGF expression in rat blood vessels, ameliorating arterial blood flow in lower limb arteriosclerosis obliterans through the Sirt1 signaling pathway.