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Background The relationship between aurora kinase A (Aurora A) expression level in the medullary thyroid carcinoma (MTC) tissue and the clinicopathological characteristics and biochemical cure of patients remains unclear. Objective To analyze the relationship between Aurora A expression level in medullary thyroid tissue and the clinicopathological characteristics of patients, to further analyze the risk factors for biochemical cure and clarify the correlation between Aurora A expression and biochemical cure. Methods A total of 90 patients with MTC who were hospitalized with MTC resection in the Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital from February 2011 to July 2019 were enrolled, the clinical data of the patients were collected, and Aurora A expression level in the tissues was detected by immunohistochemical detection, and the influencing factors of biochemical cure of MTC patients were explored by multivariate Logistic regression model. Results 62 patients with high Aurora A expression level and 28 patients with low Aurora A expression were included, 40 patients achieved biochemical cure and 18 patients experienced recurrence. There were significant differences in gender, maximum tumor length, T stage, N stage, AJCC8th clinical stage, biochemical cure, and recurrence between patients with high Aurora A expression level and low Aurora A expression level (P

Abstract Thyroid cancer (TC) is the most common endocrine tumor, amongst which anaplastic thyroid carcinoma (ATC) is the most deadly. Aurora-A usually functions as oncogenes, and its inhibitor Alisertib exerts a powerful antitumor effect in various tumors. However, the mechanism of Aurora-A in regulating TC cell energy supply remains unclear. In the present study, we demonstrated the antitumor effect of Alisertib and an association between high Aurora-A expression and shorter survival. Multi-omics data and in vitro validation data suggested that Aurora-A induced PFKFB3-mediated glycolysis to increase ATP supply, which significantly upregulated the phosphorylation of ERK and AKT. Furthermore, the combination of Alisertib and Sorafenib had a synergistic effect, further confirmed in xenograft models and in vitro. Collectively, our study provides compelling evidence of the prognostic value of Aurora-A expression and suggests that Aurora-A upregulates PFKFB3-mediated glycolysis to enhance ATP supply and promote TC progression. Combining Alisertib with Sorafenib has huge prospects for application in treating advanced thyroid carcinoma.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial‐mesenchymal transformation (EMT), thyroid differentiation‐related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor‐based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3‐mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3‐dependent manner. Finally, the METTL3‐14‐WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR‐SMARCA2‐TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation. [ABSTRACT FROM AUTHOR]

Background: BRAFV600E is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including proliferation, metastasis and immune‐escape. BRAFV600E‐mutated papillary thyroid cancer (PTC) also displays greatly reduced expression of thyroid differentiation markers, thus tendency to radioactive iodine (RAI) refractory and poor prognosis. Therefore, understanding the molecular mechanisms and main oncogenic events underlying BRAFV600E will guide future therapy development. Methods: Bioinformatics and clinical specimen analyses, genetic manipulation of BRAFV600E‐induced PTC model, functional and mechanism exploration guided with transcriptomic screening, as well as systematic rescue experiments were applied to investigate miR‐31 function within BRAFV600E‐induced thyroid cancer development. Besides, nanoparticles carrying miR‐31 antagomirs were testified to alleviate 131I iodide therapy on PTC models. Results: We identify miR‐31 as a significantly increased onco‐miR in BRAFV600E‐associated PTC that promotes tumour progression, metastasis and RAI refractoriness via sustained Wnt/β‐catenin signalling. Mechanistically, highly activated BRAF/MAPK pathway induces miR‐31 expression via c‐Jun‐mediated transcriptional regulation across in vitro and transgenic mouse models. MiR‐31 in turn facilitates β‐catenin stabilisation via directly repressing tumour suppressors CEBPA and DACH1, which direct the expression of multiple essential Wnt/β‐catenin pathway inhibitors. Genetic functional assays showed that thyroid‐specific knockout of miR‐31 inhibited BRAFV600E‐induced PTC progression, and strikingly, enhanced expression of sodium‐iodide symporter and other thyroid differentiation markers, thus promoted 131I uptake. Nanoparticle‐mediated application of anti‐miR‐31 antagomirs markedly elevated radio‐sensitivity of BRAFV600E‐induced PTC tumours to 131I therapy, and efficiently suppressed tumour progression in the pre‐clinical mouse model. Conclusions: Our findings elucidate a novel BRAF/MAPK‐miR‐31‐Wnt/β‐catenin regulatory mechanism underlying clinically BRAFV600E‐associated DTC tumourigenesis and dedifferentiation, also highlight a potential adjuvant therapeutic strategy for advanced DTC. [ABSTRACT FROM AUTHOR]

Background: We planned to explore the underlying mechanism and clinical significance of lnc-SNHG5 and RPS3 in hepatocellular carcinoma in this current study.Methods: The expression of Lnc-SNHG5 and RPS3 in HCC tissues and several cell lines were affirmed, respectively, using UALCAN, TIMER, TCGA and RT-qPCR assay. Cell proliferation ability was detected by colony formation assay and CCK8 assay. Cell apoptosis was monitored by flow cytometry assay. Next, the RPS3 expression levels and the related proteins in NFκB pathway were examined using Western blot analysis. The role of lnc-SNHG5 and RPS3 in vivo was identified by subcutaneous tumor bearing experiment.Results: Lnc-SNHG5 was significantly increased in hepatocellular carcinoma tissues and in hepatocellular carcinoma cells. Further investigation showed that up-regulated lnc-SNHG5 promoted cell viability and cell proliferation ability of SMMC-7721 cells by regulating the cell apoptosis, while down-regulation of lnc-SNHG5 revealed opposite results in QGY-7703 cells. In terms of mechanism, we found that lnc-SNHG5 interacted with RPS3. Lnc-SNHG5 regulated the NFκB pathway through RPS3 in vitro and in vivo.Conclusion: This study suggested that lnc-SNHG5 expression was signally up-regulated in hepatocellular carcinoma, and lnc-SNHG5 promoted the malignant phenotypes in vitro and in vivo via directly regulating RPS3-NFκB pathway. Lnc-SNHG5 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for HCC patients. [ABSTRACT FROM AUTHOR]

The cooperative transition of sulfur-containing pollutants of H2S/CO/H2 to the high-value chemical methyl mercaptan (CH3SH) is catalyzed by Mo-based catalysts and has good application prospects. Herein, a series of Al2O3-supported molybdenum carbide catalysts with K doping (denoted herein as K-Mo2C/Al2O3) are fabricated by the impregnation method, with the carbonization process occurring under different atmospheres and different temperatures between 400 and 600 °C. The CH4-K-Mo2C/Al2O3 catalyst carbonized by CH4/H2 at 500 °C displays unprecedented performance in the synthesis of CH3SH from CO/H2S/H2, with 66.1% selectivity and a 0.2990 g·gcat−1·h−1 formation rate of CH3SH at 325 °C. H2 temperature-programmed reduction, temperature-programmed desorption, X-ray diffraction and Raman and BET analyses reveal that the CH4-K-Mo2C/Al2O3 catalyst contains more Mo coordinatively unsaturated surface sites that are responsible for promoting the adsorption of reactants and the desorption of intermediate products, thereby improving the selectivity towards and production of CH3SH. This study systematically investigates the effects of catalyst carbonization and passivation conditions on catalyst activity, conclusively demonstrating that Mo2C-based catalyst systems can be highly selective for producing CH3SH from CO/H2S/H2. [ABSTRACT FROM AUTHOR]