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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.

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BACKGROUND: Considering the combined role of long non-coding RNA (lncRNAs)-microRNA (miRNA)-mRNA in tumorigenesis, the purpose of this study was to investigate how TNRC6C-AS1 regulates the expression of lysophosphatidic acid receptor 5 (LPAR5) by modulating miR-513c-5p, thus influencing the progression of thyroid cancer (THCA). METHODS: qRT-PCR and Western blotting were performed to detect the expression levels of TNRC6C-AS1, miR-513c-5p, and LPAR5 in THCA tissues and cell lines. The viability, proliferation, migration, and invasion were assessed using CCK-8, BrdU, wound healing, and transwell migration assays, respectively. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were used to evaluate the relationship between TNRC6C-AS1, miR-513c-5p, and LPAR5. RESULTS: TNRC6C-AS1 was highly expressed in THCA tissues, and knockout of TNRC6C-AS1 reduced the viability, proliferation, migration, and invasion of THCA cells. TNRC6C-AS1 competitively adsorbed miR-513c-5p. In addition, the biological function of TNRC6C-AS1 was blocked by knocking down the thyroid cell line TNRC6C-AS1 with miR-513c-5p inhibitor transfection. LPAR5 is the target gene for miR-513c-5p, which has the ability to eliminate the influence of miR-513c-5p on THCA cells. CONCLUSION: The TNRC6C-AS1/miR-513c-5p/LPAR5 axis is a novel signaling pathway that modulates THCA progression and may be a potential target for cancer therapy.

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BACKGROUND: Papillary thyroid microcarcinoma (PTM) belongs to papillary carcinomas whose length is about 1.0 cm. According to previous studies, FOXE1 is a transcription factor involved in the progression of papillary thyroid carcinoma (PTC). However, its detailed upstream mechanism remains unknown in PTM. OBJECTIVE: Our study aimed at detecting and verifying the up-regulation of FOXE1 in PTM cell lines. METHODS: FXOE1 expression was detected in PTM and normal cells through RT-qPCR. Loss-of-function experiments were conducted to identify the effect of silenced FOXE1 on cell proliferation, apoptosis, migration and invasion. Mechanism experiments were carried out to explore the upstream molecular mechanism of FOXE1. RESULTS: Knockdown of FOXE1 could lead to the inhibition on cell proliferation, migration and invasion while positively regulating cell apoptosis. Importantly, Yin-Yang-1 (YY1) could boost the transcription of FOXE1, thereby upregulating FOXE1. Also, the binding potential of miR-129-5p to FOXE1 was identified in PTM cells and MiR-129-5p could target FOXE1. In addition, the cellular processes in PTM were hindered with the increase of miR-129-5p expression level. CONCLUSION: Our research suggested that the up-regulation of FOXE1 is regulated by YY1 and miR-129-5p, which may contribute to PTM progression.

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AIM: To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer. METHODS: A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy. CONCLUSIONS: The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).

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