Seven Sirtuin family members (SIRT1-7), comprising a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases, are key proteins that regulate multiple physiological processes. SIRT2 was recently reported to play an important role in carcinogenesis. However, its role in non-small cell lung cancer (NSCLC) has not yet been investigated. In this study, we analyzed the expression pattern of SIRT2 in NSCLC tissues from clinical patients and in cell lines, and found that SIRT2 was significantly down-regulated at both the mRNA and protein levels in tumor than non-tumor tissues or cells, which were corroborated by the NSCLC tissue microarray results. Overexpression of SIRT2 in A549 and H1299 cells caused cell proliferation inhibition, cell apoptosis induction and cell cycle arrest. Further analysis showed that SIRT2 overexpression increased the ROS (reactive oxygen species) production and p27 levels. Moreover, up-regulation of SIRT2 in NSCLC cells increased the sensitivity to Cisplatin treatment. Taken together, our results implied that down-regulation of SIRT2 was associated with NSCLC, and regulation of SIRT2 might be an important target for NSCLC therapy.
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http://dx.doi.org/10.1016/j.lungcan.2013.05.013 | DOI Listing |
Int Ophthalmol
January 2025
Department of Ophthalmology, Xingtai People's Hospital, Xingtai, 054001, Hebei, China.
Background: Retinopathy of prematurity (ROP) is a major cause of childhood blindness worldwide, highlighted by retinal neovascularization. Ubiquitin is present throughout the retina. The deubiquitinating enzyme ubiquitin-specific protease 39 (USP39) has been reported to be involved in angiogenesis.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Rd, Changsha, Hunan, 410013, China.
Diabetic nephropathy (DN) is a serious complication of diabetes, and inflammation plays a crucial role. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, which is involved in the regulation of cell metabolism, proliferation and longevity through deacetylation. Our previous research showed a positive correlation between urinary SIRT2 levels and renal injury markers in DN patients.
View Article and Find Full Text PDFMol Genet Genomics
January 2025
Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Recent therapeutic strategies have highlighted the potential of β-hydroxybutyrate (BHB) and α-ketoglutarate (α-KG) as effective anticancer agents, particularly for colon cancer. These metabolites can modulate cellular metabolism and induce epigenetic changes, inhibiting tumor growth. Nonetheless, certain cancer cells may utilize ketone bodies, like BHB as nutrient sources under hypoxic conditions, potentially reducing treatment efficacy.
View Article and Find Full Text PDFElife
January 2025
Translational Science and Therapeutics Division, Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States.
The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In , the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of , a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, Duke Eye Center, Duke University, Durham, North Carolina, United States.
Purpose: To study the roles of tubulin acetylation and cyclic mechanical stretch (CMS) in trabecular meshwork (TM) cells and their impact on outflow pathway physiology and pathology.
Methods: Primary TM cell cultures were subjected to CMS (8% elongation, 24 hours), and acetylated α-tubulin at lysine 40 (Ac-TUBA4) was assessed by western blotting and immunofluorescence. Enzymes regulating tubulin acetylation were identified via siRNA-mediated knockdowns of ATAT1, HDAC6, and SIRT2.
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