Bioinformatic Analysis of the Effect of the Sirtuin Family on Differentiated Thyroid Carcinoma

Abstract

A growing body of experimental evidence suggests that sirtuins (SIRTs) are associated with tumorigenesis in differentiated thyroid cancer (DTC). Nevertheless, the involvement of SIRTs in the pathogenesis of DTC and their clinical value remain ill-defined and should be thoroughly examined. We explored the transcription of SIRTs and survival data of patients with DTC by the systematic utilization of bioinformatics to analyze data of publicly accessible databases including Oncomine, cBioPortal, Kaplan-Meier Plotter, Gene Expression Profiling Interactive Analysis (GEPIA), Protein Atlas, LinkedOmics, and GSCALite. The examination of gene expression profiles showed that SIRT2, SIRT3, SIRT4, SIRT5, and SIRT6 were downregulated in DTC tissues compared with the normal thyroid tissues. The decreased expression levels of SIRT2, SIRT4, and SIRT5 were correlated with advanced tumor stages. The survival results showed that the increased SIRT4 mRNA expression level was associated with improved overall survival (OS) in the DTC patients. In addition, patients with DTC with high SIRT2, SIRT3, SIRT4, and SIRT5 mRNA levels had higher disease-free survival (DFS). These results showed that SIRT2, SIRT3, SIRT4, SIRT5, and SIRT6 are potential targets for precise treatment of DTC patients and that SIRT2, SIRT3, SIRT4, and SIRT5 are novel potential biomarkers for the prognosis of DTC.

Comprehensive Analysis of the Oncogenic, Genomic Alteration, and Immunological Landscape of Cation-Chloride Cotransporters in Pan-Cancer

“…To further investigate the role of KCC2 (SLC12A5) and NKCC1 (SLC12A2) in pan-cancers, we analyzed mutation abundance and frequency of KCC2/NKCC1 in pan-cancer using cBioportal for Cancer Genomics ( ) ( 25 ). A total of 48,834 cancer samples with available DNA variation, including mutations, copy number variation (CNV), somatic number variation (SNV), and profiles from 188 independent curated of non-redundant cohorts were enrolled.…”

Novel 1,4-Dihydropyridines as Specific Binders and Activators of SIRT3 Impair Cell Viability and Clonogenicity and Downregulate Hypoxia-Induced Targets in Cancer Cells

“…First, older evidence showed that SIRT3 was highly expressed in DTC compared to benign thyroid tumors, while Wang et al showed that MiR-1225-5p might trigger DTC cell proliferation and metastasis by targeting SIRT3 . Newer findings by Yao and Wang, in a more clinical setting, indicate the opposite, showing that mRNA expression levels of SIRT3 decreased in their DTC model compared to healthy cells and that patients with high SIRT3 expression had a longer disease-free survival …”

“…24 Newer findings by Yao and Wang, in a more clinical setting, indicate the opposite, showing that mRNA expression levels of SIRT3 decreased in their DTC model compared to healthy cells and that patients with high SIRT3 expression had a longer disease-free survival. 25 SIRT3 is not only involved in cancer but also in infectious, 26,27 heart, 28 kidney, 29 metabolic, 30,31 and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, as well as in stroke and traumatic brain injury. 32 A recent study by Yan et al stated that SIRT3 is very likely to play a crucial role in the development of neuropathic pain.…”

Exploring the Multi-Faceted Role of Sirtuins in Glioblastoma Pathogenesis and Targeting Options

“…A growing body of experimental evidence has implicated SIRTs in the regulation of pivotal cellular processes involved in cancer initiation and progression [ 14 , 15 , 16 , 17 , 106 ]. Although their expression is quite variable among tumor types and may act either as tumor suppressors or promoters depending on the cellular context, some SIRTs have shown clinical relevance with prognostic significance, biomarker potential, and association with drug resistance [ 14 , 15 , 16 , 17 ]. Emerging data have also implicated SIRTs in various aspects of glioma tumorigenesis, including proliferation, apoptosis, autophagy, stemness, angiogenesis, and metastasis, and are discussed in the following sections.…”

“…Eighteen HDACs have been identified thus far and classified into four classes [ 9 ]. Class III HDACs, also known as sirtuins (SIRTs) were originally investigated as potential therapeutic targets in age-related and neurodegenerative diseases [ 10 , 11 ], inflammatory disorders [ 12 ], muscular diseases [ 13 ], and recently, in different cancer types [ 14 , 15 , 16 , 17 ], including GB. The role of SIRTs as regulators of gliomagenesis is currently under thorough research with significant data.…”