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

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM European Thyroid Journal Pub Date : 2024-09-16 Print Date: 2024-10-01 DOI:10.1530/ETJ-24-0079
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
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Abstract

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.

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Sirtuin 4 水平降低会促进甲状腺乳头状癌的细胞增殖和侵袭
研究目的本研究探讨了Sirtuin 4(Sirt4)(一种NAD+依赖性去乙酰化酶)对甲状腺乳头状癌(PTC)的增殖和进展的影响:方法:分析癌症基因组图谱(TCGA)中的数据,确定甲状腺癌中Sirt4的表达。随后,在205份PTC组织样本中检测了Sirt4表达与临床特征之间的相关性。利用三种人类甲状腺癌细胞系(B-CPAP、TPC-1 和 SNU-790)进行了体外实验,以评估调控 Sirt4 表达对细胞生长、凋亡、侵袭和迁移的影响。此外,还在异种移植小鼠模型中进行了体内实验:GEO和TCGA数据表明,Sirt4在甲状腺癌中的表达量较低,Sirt4的下调与总生存率低有关。在我们的 PTC 组织中,Sirt4 的阳性表达与囊外扩展的减少有关。在使用三种人类甲状腺癌细胞系进行的体外实验中,Sirt4 的过表达会降低细胞的存活率、克隆生成潜能、侵袭和迁移能力,并诱导细胞凋亡和增加活性氧水平。Sirt4过表达会上调E-cadherin,下调N-cadherin,这表明它可能参与了上皮-间质转化的调控。这些发现通过异种移植小鼠模型在体内得到了证实:本研究为了解 Sirt4 在调控 PTC 病理进展中的潜在作用提供了新的视角。数据表明,Sirt4 在 PTC 中通过抑制生长、存活和侵袭潜能发挥抑制肿瘤的作用。未来的研究应探讨 Sirt4 发挥这些作用的分子机制。
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来源期刊
European Thyroid Journal
European Thyroid Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
6.70
自引率
2.10%
发文量
156
期刊介绍: The ''European Thyroid Journal'' publishes papers reporting original research in basic, translational and clinical thyroidology. Original contributions cover all aspects of the field, from molecular and cellular biology to immunology and biochemistry, from physiology to pathology, and from pediatric to adult thyroid diseases with a special focus on thyroid cancer. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research. The journal will further publish formal guidelines in the field, produced and endorsed by the European Thyroid Association.
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