ABSTRACT
Introduction: SIRTs (Sirtuins) are class III histone deacetylase enzymes that use NAD+ as a co-substrate for their enzymaticactivities. In mammals, there are seven sirtuin proteins (SIRT1–SIRT7) among which SIRT4, SIRT3 and SIRT5 are mitochondrialsirtuins that regulate enzymes and other mitochondrial proteins to coordinate oxidative production of ATP with the availability ofenergy in the diet. SIRT4 is known to have tumor suppression activity in many human cancers. However, the role of SIRT4 inoral squamous cell carcinoma is not known. It is present at higher levels under nutrient-rich conditions, and inhibits glutaminecatabolism through ADP-ribosylation and hence repression of glutamate dehydrogenase (GDH) activity, a rate-limiting enzymein glutamine catabolism. Due to higher requirement of energy and bio-molecules for proliferation, cancer cell often resort tovarious metabolic pathways that are otherwise uncommon in normal cells. One of such mechanism is switching to Glutaminemetabolism. SIRT4 acts as a tumor suppressor by repressing glutamine utilisation by cells.Purpose: Study the role of SIRT4 in oral squamous cell carcinoma and evaluate its tumor suppressor role.Method: Here we studied expression of SIRT4 in oral cancer tissues by immuohistochemistry and compared it with that ofnormal tissue.Results: SIRT 4 was seen to significantly down regulated in oral squamous carcinoma.Conclusion: The present study suggests SIRT4 as a marker of tumor aggressiveness and as a therapeutic target for OSCC.
ABSTRACT
Silent information regulators are a family of highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases and has seven members (Sirt1-7). Silent information regulator 4 (Sirt4), localized in the mitochondria, possesses the activity of deacetylase, ADP-ribosyltransferase, NAD+-dependent lipoamidase, and deacylase, participates in post-translational modification of mitochondrial proteins, and regulates multiple metabolic processes. Since metabolic dysfunction is closely associated with liver diseases, the role and regulatory mechanism of Sirt4 in liver diseases has attracted more and more attention. This article elaborates on the role of Sirt4 in viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma, in order to provide new perspectives for the prevention and treatment of these liver diseases.
ABSTRACT
Silent information regulators are a family of highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases and has seven members (Sirt1-7). Silent information regulator 4 (Sirt4), localized in the mitochondria, possesses the activity of deacetylase, ADP-ribosyltransferase, NAD+-dependent lipoamidase, and deacylase, participates in post-translational modification of mitochondrial proteins, and regulates multiple metabolic processes. Since metabolic dysfunction is closely associated with liver diseases, the role and regulatory mechanism of Sirt4 in liver diseases has attracted more and more attention. This article elaborates on the role of Sirt4 in viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma, in order to provide new perspectives for the prevention and treatment of these liver diseases.