Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma

Hyun-Jin Lee; Young-Sool Hah; So Young Cheon; Seong Jun Won; Chae Dong Yim; Somi Ryu; Seung-Jun Lee; Ji Hyun Seo; Jung Je Park

doi:10.1530/ETJ-24-0079

European Thyroid Journal (Oct 2024)

Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma

Hyun-Jin Lee,
Young-Sool Hah,
So Young Cheon,
Seong Jun Won,
Chae Dong Yim,
Somi Ryu,
Seung-Jun Lee,
Ji Hyun Seo,
Jung Je Park

Affiliations

Hyun-Jin Lee: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, South Korea
Young-Sool Hah: Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, South Korea
So Young Cheon: Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, South Korea
Seong Jun Won: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, South Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea
Chae Dong Yim: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, South Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea
Somi Ryu: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, South Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea
Seung-Jun Lee: Department of Convergence of Medical Sciences, Gyeongsang National University, Jinju, South Korea
Ji Hyun Seo: Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea; Department of Pediatrics, Gyeongsang National University College of Medicine, Jinju, South Korea
Jung Je Park: Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, South Korea; Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, South Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea

DOI: https://doi.org/10.1530/ETJ-24-0079
Journal volume & issue: Vol. 13, no. 5
pp. 1 – 11

Abstract

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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: Gene Expression Omnibus (GEO) and TCGA data indicated that SIRT4 expression is lower in thyroid cancer and SIRT4 downregulation is associated with poor overall survival. In 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 the 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.

Published in European Thyroid Journal

ISSN: 2235-0802 (Online)
Publisher: Bioscientifica
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: https://etj.bioscientifica.com/

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