Sterol synthesis is a highly complex and integrated pathway in mammals. In the present review, we briefly summarize the main steps of this pathway, especially concerning its main rate-limiting enzymes, HMG-CoA reductase (HMGCR) and squalene epoxidase (SQLE), in relation with cancer. We focus on studies reporting key findings linking cholesterol with cancer. The inhibition of HMGCR and SQLE to prevent and inhibit cancer are reviewed. Finally, a pan-cancer review of publicly available data on genomic aberrations in the main enzymes involved in sterol biosynthesis and their transcription factors is reported, providing hitherto unexplored findings that may be the subject of future research in cancer metabolomics and tumor targeted treatment.Colorectal cancer ranks among the top three most frequent malignancies in the world. While overall incidence and mortality of colorectal cancer has substantially decreased in recent years, tumor subtypes with poor response rates to standard antiproliferative therapies remain particularly challenging. Hypoxia in the microenvironment of solid tumors is associated with malignant progression, e.g. local invasion, systemic spread and therapy resistance. A detailed molecular understanding of hypoxia's role for the pathobiology of colorectal cancer is a prerequisite to design and evaluate the consequences of interference with hypoxic signaling for the progression of this cancer type. Here, we summarize the current knowledge about the role of hypoxia-inducible factor 1, an essential molecular mediator of the hypoxic response, for colorectal cancer pathogenesis. Special attention is given to intestinal microbiota, gut barrier integrity and chronic inflammation as these are of pivotal importance for intestinal tumorigenesis and noticeably associated with hypoxic signaling.Estrogen hormones protect against colorectal cancer (CRC) and a preventative role of estrogen receptor beta (ERβ) on CRC has been supported using full knockout animals. However, it is unclear through which cells or organ ERβ mediates this effect. To investigate the functional role of intestinal ERβ during colitis-associated CRC we used intestine-specific ERβ knockout mice treated with azoxymethane and dextran sodium sulfate, followed by ex vivo organoid culture to corroborate intrinsic effects. We explored genome-wide impact on TNFα signaling using human CRC cell lines and chromatin immunoprecipitation assay to mechanistically characterize the regulation of ERβ. Increased tumor formation in males and tumor size in females was noted upon intestine-specific ERβ knockout, accompanied by enhanced local expression of TNFα, deregulation of key NFκB targets, and increased colon ulceration. Unexpectedly, we noted especially strong effects in males. We corroborated that intestinal ERβ protects against TNFα-induced damage intrinsically, and characterized an underlying genome-wide signaling mechanism in CRC cell lines whereby ERβ binds to cis-regulatory chromatin areas of key NFκB regulators. Our results support a protective role of intestinal ERβ against colitis-associated CRC, proposing new therapeutic strategies.Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally targeted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM.GCN5, conserved from yeast to humans, and the vertebrate specific PCAF, are lysine acetyltransferase enzymes found in large protein complexes. Both enzymes have well documented roles in the histone acetylation and the concomitant regulation of transcription. However, these enzymes also acetylate non-histone substrates to impact diverse aspects of cell physiology. Here, I review our current understanding of non-histone acetylation by GCN5 and PCAF across eukaryotes, from target identification to molecular mechanism and regulation. I focus mainly on budding yeast, where Gcn5 was first discovered, and mammalian systems, where the bulk of non-histone substrates have been characterized.  https://www.selleckchem.com/products/VX-770.html  I end the review by defining critical caveats and open questions that apply to all models.Eukaryotic genomes are maintained within DNA-protein complexes called chromatin. Post-translational modification of chromatin proteins, and especially acetylation of the core histone amino-terminal tails, has long been associated with chromatin assembly and the regulation of gene expression. It is now well accepted that an elaborate array of enzymes are responsible for posttranslational chromatin marks including acetylation and methylation among others and that together they have profound effects on gene regulation. However, this was not always the case. Here we describe the events surrounding the initial identification of GCN5 as a histone acetyltransferase from Tetrahymena thermophila and the discovery that it is an ortholog of a transcription co-activator complex in yeast. This discovery was the first to directly link a well-described transcription factor and histone modifying activity.