Transcription Factor Zbtb20 as a Regulator of Malignancy and Its Practical Applications.

Zbtb20 (zinc finger and BTB domain-containing protein 20) is a transcription factor with a zinc finger DNA binding domain and a BTB domain responsible for protein-protein interaction. Recently, this TF has received attention because new data showed its pivotal involvement in normal neural development and its regulatory effects on proliferation and differentiation in different tissues. Zbtb20 was shown to increase proliferation and migration and confer resistance to apoptosis in the contexts of many malignant tumors like hepatocellular carcinoma, non-small-cell lung carcinoma, gastric adenocarcinoma, glioblastoma multiforme, breast cancer, and acute myeloid leukemia. The involvement of Zbtb20 in tumor biology is best studied in hepatocellular carcinoma, where it is a promising candidate as an immunohistochemical tumor marker or may be used in patient screening. Here we review the current data connecting Zbtb20 with malignant tumors.

Circulating Histones to Detect and Monitor the Progression of Cancer.

Liquid biopsies have emerged as a minimally invasive cancer detection and monitoring method, which could identify cancer-related alterations in nucleosome or histone levels and modifications in blood, saliva, and urine. Histones, the core component of the nucleosome, are essential for chromatin compaction and gene expression modulation. Increasing evidence suggests that circulating histones and histone complexes, originating from cell death or immune cell activation, could act as promising biomarkers for cancer detection and management. In this review, we provide an overview of circulating histones as a powerful liquid biopsy approach and methods for their detection. We highlight current knowledge on circulating histones in hematologic malignancies and solid cancer, with a focus on their role in cancer dissemination, monitoring, and tumorigenesis. Last, we describe recently developed strategies to identify cancer tissue-of-origin in blood plasma based on nucleosome positioning, inferred from nucleosomal DNA fragmentation footprint, which is independent of the genetic landscape.

Liquid Liver Biopsy for Disease Diagnosis and Prognosis.

Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotransferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, posing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and monitoring of liver diseases by detecting disease-associated particles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regulating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circulation, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection methods.

Distribution, Function, and Expression of the Apelinergic System in the Healthy and Diseased Mammalian Brain.

Apelin, a peptide initially isolated from bovine stomach extract, is an endogenous ligand for the Apelin Receptor (APLNR). Subsequently, a second peptide, ELABELA, that can bind to the receptor has been identified. The Apelin receptor and its endogenous ligands are widely distributed in mammalian organs. A growing body of evidence suggests that this system participates in various signaling cascades that can regulate cell proliferation, blood pressure, fluid homeostasis, feeding behavior, and pituitary hormone release. Additional research has been done to elucidate the system's potential role in neurogenesis, the pathophysiology of Glioblastoma multiforme, and the protective effects of apelin peptides on some neurological and psychiatric disorders-ischemic stroke, epilepsy, Parkinson's, and Alzheimer's disease. This review discusses the current knowledge on the apelinergic system's involvement in brain physiology in health and disease.

Expression of Transcription Factor ZBTB20 in the Adult Primate Neurogenic Niche under Physiological Conditions or after Ischemia.

The Zbtb20 gene encodes for a transcription factor that plays an important role in mammalian cortical development. Recently, its expression was reported in the adult mouse subventricular zone (SVZ), a major neurogenic niche containing neural stem cells throughout life. Here, we analyzed its expression in the adult primate anterior SVZ (SVZa) and rostral migratory stream (RMS) using macaque monkeys (Macaca fuscata). We report that the majority of Ki67+ cells, 71.4% in the SVZa and 85.7% in the RMS, co-label for ZBTB20. Nearly all neuroblasts, identified by their Doublecortin expression, were positive for ZBTB20 in both regions. Nearly all GFAP+ neural stem cells/astrocytes were also positive for ZBTB20. Analysis of images derived from a public database of gene expression in control/ischemic monkey SVZa, showed evidence for ZBTB20 upregulation in postischemic monkey SVZa. Furthermore, the co-localization of ZBTB20 with Doublecortin and Ki67 was increased in the postischemic SVZa. Our results suggest that ZBTB20 expression is evolutionarily conserved in the mammalian neurogenic niche and is reactive to ischemia. This opens the possibility for further functional studies on the role of this transcription factor in neurogenesis in primates.