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Luciana Puleo Endocrine Unit, Department of Clinical and Experimental Medicine

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Laura Agate Endocrine Unit, Department of Clinical and Experimental Medicine

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Irene Bargellini Department of Vascular and Interventional Radiology

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Giuseppe Boni Regional Center of Nuclear Medicine

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Paolo Piaggi Endocrine Unit, Department of Clinical and Experimental Medicine

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Claudio Traino Regional Center of Nuclear Medicine

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Tommaso Depalo Regional Center of Nuclear Medicine

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Giulia Lorenzoni Department of Vascular and Interventional Radiology

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Francesca Bianchi Regional Center of Nuclear Medicine

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Duccio Volterrani Regional Center of Nuclear Medicine

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Sandra Brogioni Endocrine Unit, Department of Clinical and Experimental Medicine

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Valeria Bottici Endocrine Unit, Department of Clinical and Experimental Medicine

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Maurizia Rossana Brunetto Hepatology Unit, University of Pisa, Pisa, Italy

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Barbara Coco Hepatology Unit, University of Pisa, Pisa, Italy

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Eleonora Molinaro Endocrine Unit, Department of Clinical and Experimental Medicine

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Rossella Elisei Endocrine Unit, Department of Clinical and Experimental Medicine

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(such as embolization or chemoembolization) and systemic therapy can be the only therapeutic options ( 2 ). In last decades, transarterial radioembolization (TARE), also known as selective internal radiation therapy (SIRT) ( 6 , 7 ), with microspheres

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Hyun-Jin Lee H Lee, Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Korea (the Republic of)

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Young-Sool Hah Y Hah, Gyeongsang National University Hospital, Jinju, Korea (the Republic of)

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So Young Cheon S Cheon, Gyeongsang National University Hospital, Jinju, Korea (the Republic of)

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Seong Jun Won S Won, Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Korea (the Republic of)

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Chae Dong Yim C Yim, Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Korea (the Republic of)

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Somi Ryu S Ryu, Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Korea (the Republic of)

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Seong-Jun Lee S Lee, Department of Convergence of Medical Sciences, Gyeongsang National University, Jinju, Korea (the Republic of)

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Ji Hyun Seo J Seo, Gyeongsang National University, Jinju, Korea (the Republic of)

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Jung Je Park J Park, Department of Otolaryngology, Gyeongsang National University, Jinju, 52727, Korea (the Republic of)

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Objective: This study examined the effect of Sirtuin 4 (Sirt4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC).

Methods: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify Sirt4 expression in thyroid cancer. Subsequently, the correlation between Sirt4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated Sirt4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model.

Results: GEO and TCGA data indicated that Sirt4 expression is lower in thyroid cancer and Sirt4 downregulation is associated with poor overall survival. In our PTC tissues, positive Sirt4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of Sirt4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. Sirt4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial–mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model.

Conclusion: This study provides novel insight into the potential contribution of Sirt4 to regulation of the pathological progression of PTC. The data suggest that Sirt4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of Sirt4.

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João Anselmo Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo, Ponta Delgada, Portugal

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Carolina M. Chaves Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo, Ponta Delgada, Portugal

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involved the regulation of TH target genes [ 30 ]. SIRT1 (the first of 7 different sirtuin enzymes) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that removes the acetyl groups from proteins, such as histones, thereby affecting the

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Nandhini Lakshmana Perumal Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

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Jayakumar Selvi Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

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Kalyani Sridharan Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

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Jayaprakash Sahoo Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

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Sadishkumar Kamalanathan Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

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. Glycemic status in hyperthyroid subjects . Mymensingh Med J . 2004 Jan ; 13 ( 1 ): 71 – 5 . 14747791 1022-4742 3 Suh JH , Sieglaff DH , Zhang A , Xia X , Cvoro A , Winnier GE , et al. SIRT1 is a direct coactivator of thyroid

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Hicham Benabdelkamel Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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Malak A Jaber Pharmaceutical Medicinal Chemistry & Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan

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Lina A Dahabiyeh Division of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, Jordan

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Afshan Masood Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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Reem H Almalki Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia

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Mohthash Musambil Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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Anas M Abdel Rahman Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Department of Medicine, College of Medicine and King Saud Medical City, King Saud University, Riyadh, Saudi Arabia

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Assim A Alfadda Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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.ejim.2016.03.028 ) 44 Chau MD Gao J Yang Q Wu Z & Gromada J . Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway . Proceedings of the National Academy of Sciences of the United States of

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Josef Köhrle Institut für Experimentelle Endokrinologie, Charité Campus Virchow-Klinikum (CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

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affected by pharmacological daily doses of 10 and 25 mg/kg 3-T1AM, and SIRT4- and SIRT6-dependent genes responded in the liver after 3-T1AM administration in subchronic protocols using female CD1 mice [188]. Analysis of 3-T1AM concentration in various

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