Abstract
Sirtuins (SIRTs) are members of the silent information regulator-2 family. They are a conserved family of nicotinamide adenine dinucleotide-dependent protein lysine deacylases. SIRTS are involved in intricate cellular processes. There are seven subtypes of SIRTs (1–7) in mammals. SIRT4 is located mainly in mitochondria and has various catalytic activities. These enzyme activities give it a diverse range of important biologic functions, such as energy metabolism, oxidative stress, and aging. Cancer is characterized as reprogramming of energy metabolism and redox imbalance, and SIRT4 can affect tumorigenesis. Here, we review the structure, localization, and enzyme activity of SIRT4 and its role in various neoplasms.
Highlights
Cancer has become the first or second most prevalent cause of premature death in ~100 countries [1]
Further studies showed that inhibition of glutamine metabolism by SIRT4 led to positive regulation of E-cadherin expression
Thyroid Cancer Analyses of tissue samples from 89 patients with thyroid cancer by Chen and colleagues showed that expression of SIRT4 protein decreased significantly compared with that in normal tissue, but there was no significant correlation with clinicopathologic features
Summary
Cancer has become the first or second most prevalent cause of premature death in ~100 countries [1]. SIRT4 can inhibit glutamine metabolism in mitochondria after DNA damage and regulate cell-cycle progression and genomic fidelity in response to DNA damage. IHC analyses showed that SIRT4 expression was down-regulated significantly in tumor tissues compared with that in paracancerous tissues. Those results suggested that SIRT4 may have a tumorinhibitory role in pericarcinomatous tissues of HCC by inhibiting the development and migration of tumor cells and, improving the prognosis of patients.
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