Rabbit Anti-Human Histone H4 (a.a. 6-55) Polyclonal antibody

The primary cilium is a non-motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are essential for proliferating cells, and several signalling pathways are responsible for their regulation. In fact, the primary cilium is a central hub for numerous signalling pathways implicated in a variety of biological processes, such as the Hedgehog, mammalian target of rapamycin and Wnt pathways. Loss of primary cilia has been recently correlated with different types of tumours, including pancreatic ductal adenocarcinoma (PDAC). K-Ras and HDAC2 were recently identified as possible ciliogenesis regulators in PDAC, likely acting through Aurora A kinase (AURKA) which, in turn, controls inositol polyphosphate-5-phosphatase E. However, the exact molecular mechanisms underlying this regulatory effect remain to be fully elucidated. In the present study, the regulation of the main genes involved in primary cilia assembly/resorption was reconstructed showing the links with the Hedgehog and phosphoinositide 3-kinase/AKT pathways. Finally, by analysing gene expression databases, the regulatory genes that have high probability to be associated with prognosis, histological grade and pathological stage in patients with PDAC have been highlighted. However, further experimental studies are required to reach definitive conclusions on the roles of these genes. Improving our understating of ciliogenesis and its regulators may help develop ciliotherapies using histone deacetylase and AURKA inhibitors, which may induce re-differentiation of tumour cells into normal cells by reducing tumour growth or inducing apoptosis of cancer cells.

The aberrant expression of long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been previously associated with myocardial ischemia-reperfusion injury (MIRI), but the underlying molecular mechanisms remain elusive. The current study aimed to clarify the functional role of TUG1/microRNA (miR)-340/histone deacetylase 4 (HDAC4)/beta-catenin/glucose transporter type 1 (GLUT1) axes in MIRI. The database-based analyses performed predicted the downstream factors of lncRNA TUG1. In the MIRI mouse models and hypoxia/reoxygenation (H/R)-induced cardiomyocyte models, the expression of TUG1/miR-340/HDAC4/beta-catenin/GLUT1 was manipulated to examine their effects on the infarction area, cardiomyocyte viability and apoptosis employing the Evans blue/TTC double staining, CCK-8 and TUNEL assays. Furthermore, the dual luciferase reporter and RIP assays verified the binding affinity of miR-340 to TUG1 and HDAC4. Subsequently, a negative correlation between miR-340 and TUG1 or HDAC4 expression was identified in myocardial tissues of MIRI mice and H/R-induced cardiomyocyte models, along with a positive correlation between TUG1 and HDAC4. Additionally, it was established that TUG1 bound to miR-340, and miR-340 targeted HDAC4. TUG1 upregulated HDAC4 expression, thereby promoting MIRI in the mouse models. HDAC4 was proven to repress the expression of beta-catenin and its target gene GLUT1. Moreover, the in vivo experiments validated that the inhibition of TUG1/miR-340/HDAC4/beta-catenin/GLUT1 axes alleviated MIRI in mice. Collectively, the current study uncovered the role of TUG1/miR-340/HDAC4/beta-catenin/GLUT1 axes in MIRI mouse models and H/R-induced cardiomyocyte models which may be a potential therapeutic target for MIRI treatment.