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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]

Gene therapy has been adapted for improving malignant tumor treatment. However, pharmacotherapies targeting cancer remain limited and are generally inapplicable for rare disease patients. Oleanolic acid (OA) is a plant‐derived triterpenoid that is frequently used in Chinese medicine as a safe but slow‐acting treatment for many disorders. Here, the congruent pharmacological activities of OA and CRISPR‐dCas9 in targeting AURKA or KDM1A and improving disease‐specific prognosis and used a synthetic‐biology‐inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs are utilized. In particular, the OA‐triggered CRISPR‐dCas9 transcriptional repression system rapidly and simultaneously attenuated lung and thyroid cancer. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficiencies of single therapeutics. [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: Currently, endoscopic‐assisted lateral neck dissection (EALND) is performed to reduce postoperative scarring of the anterior neck. This study aimed to compare surgical outcomes between EALND and conventional open lateral neck dissection (COLND) for papillary thyroid carcinoma (PTC) with lateral lymph node metastases (LNM). Methods: The study reviewed 103 PTC patients who were classified on the basis of surgical type and statistically compared using propensity score matching analysis. Results: The mean operation time is longer, and the cost of surgery is higher in the EALND group than COLND group (all p < 0.05). The numbers of retrieved and positive level II LNs, the rate of level II LNs detection between two groups do not differ significantly (all p > 0.05). The incidence of postoperative neck numbness is lower, and patients are more satisfied with postoperative neck scarring in the EALND group than COLND group (all p < 0.05). The common complications of two groups are transient recurrent laryngeal nerve injury and transient hypoparathyroidism. Conclusions: EALND is safe and feasible compared with COLND. The incision is more aesthetically satisfactory, which makes EALND a surgical approach for PTC patients with lateral LNM. Level of Evidence: 3 Laryngoscope, 134:2221–2227, 2024 [ABSTRACT FROM AUTHOR]