SIRT2 is a NAD ⁺ ‐dependent deacetylase that deacetylates a diverse array of protein substrates and is involved in many cellular processes, including regulation of inflammation. However, its precise role in the inflammatory process has not completely been elucidated. Here, we identify heat‐shock protein 90α (Hsp90α) as novel substrate of SIRT2. Functional investigation suggests that Hsp90 is deacetylated by SIRT2, such that overexpression and knock‐down of SIRT2 altered the acetylation level of Hsp90. This subsequently resulted in disassociation of Hsp90 with glucocorticoid receptor (GR), and translocation of GR to the nucleus. This observation was further confirmed by glucocorticoid response element (GRE)‐driven reporter assay. Nuclear translocation of GR induced by SIRT2 overexpression repressed the expression of inflammatory cytokines, which were even more prominent under lipopolysaccharide (LPS) stimulation. Conversely, SIRT2 knock‐down resulted in the up‐regulation of cytokine expression. Mutation analysis indicated that deacetylation of Hsp90 at K294 is critical for SIRT2‐mediated regulation of cytokine expression. These data suggest that SIRT2 reduces the extent of LPS‐induced inflammation by suppressing the expression of inflammatory factors via SIRT2‐Hsp90‐GR axis.

Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet been defined. As a bHLH transcription factor, Twist1 exerts its activity by forming homo- or heterodimers with other factors. In this study, we showed Twist1 restricts adipogenesis through PPARγ. Expression of various differentiation markers (including PPARγ and adiponectin) and triglyceride-containing lipid droplets were decreased with overexpression of Twist1. Pathway enrichment analysis of RNA-seq data showed that differentially expressed genes (DEGs) caused by Twist1 overexpression were significantly related to lipolysis and PPARγ signaling. This implicates that Twist1 plays important regulatory roles in these processes. ChIP and dual luciferase assays showed that Twist1 could bind either PPARγ or adiponectin promoter to repress their respective transcription or directly to PPARγ protein to regulate its transcriptional activity. Furthermore, Twist1 directly interacted RXRα, which usually forms heterodimer with PPARγ to regulate adipogenesis. Taken together, our results suggest that Twist1 is an inhibitory modulator of adipogenesis and its function is likely through direct interaction with PPARγ protein or its gene promoter.

Introduction: ZnO quantum dots (QDs) have drawn much attention recently as they are Cd-free, low-cost, and have excellent optical properties. With the expanded production and application of ZnO nanoparticles, concerns about their potential toxicity have also been raised. Materials and Methods: We used RNA sequencing (RNA-seq) to analyze the global gene expression of liver and lung tissues after ZnO QDs treatment. Differentially expressed genes (DEGs) were screened, with a fold change > 1.5 and padj < 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and padj < 0.05 was considered significantly enriched. The RNA-seq results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 47 and 218 genes were significantly differentially expressed in the liver and lung. Eight GO terms were enriched in the liver and lung, and retinol metabolism and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were shared in different tissues. Discussion: According to DEGs and pathway enrichment analyses, inflammation might be induced in liver and lung tissues after intravenous injection of ZnO QDs. These findings will be helpful for future research and application of ZnO QDs.

Esophageal cancer (ESCA) is the sixth leading cause of cancer-related mortality worldwide. Despite the significant impact, the molecular mechanisms underlying its initiation and progression remain poorly understood. In this study, we identified mircoRNA miR-193b-3p as a critical regulator of ESCA progression and the Remodeling and Spacing Factor 1 (RSF1) as an essential target of miR-193b-3p. Analysis of the TCGA_ESCA dataset and RT-qPCR experiments revealed that RSF1 levels are significantly elevated in ESCA and inversely correlated with miR-193b-3p levels. Using a dual-luciferase reporter assay, as well as transfection of miR-193-3p mimics or inhibitors, we confirmed RSF1 as a direct target of miR-193b-3p in ESCA cells. Transfection of miR-193b-3p suppresses ESCA cell proliferation, migration, and invasion. These effects were partially reversed by exogenous RSF1 expression. Injection of AgomiR-193b-3p into mice bearing ESCA xenografts impeded tumor growth. These findings underscore the critical role of the miR-193b-3p/RSF1 axis in esophageal cancer progression.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy, ranking eleventh in incidence and seventh in mortality globally. Remodeling and Spacing factor 1 (RSF1), a chromatin remodeling factor, is frequently overexpressed in various tumors and correlates with poor prognosis. This study, combining public database analysis and clinical sample validation, reveals significantly elevated RSF1 expression in ESCC tumor tissues, confirmed further in an ESCC orthotopic model. Functional assays show that RSF1 knockout (KO) significantly inhibits ESCC cell proliferation, migration, invasion, and in vivo tumor growth, while reintroducing RSF1 restores its oncogenic effects. Proteomic analysis highlights that RSF1 KO disrupts pathways associated with cell cycle control, apoptosis, and focal adhesion. Experimentally, RSF1 KO induces apoptosis and G2/M arrest, establishing its essential role in ESCC progression. Collectively, these findings establish RSF1 as an oncogenic driver and a promising therapeutic target in ESCC.