HOX Genes and Oncogenesis

Abstract

Class I homeobox genes are a family of transcription factors involved in human development, in the regulation of the cell memory program. Several HOX genes control the normal hematopoietic processes; recent evidence has demonstrated that deregulation of HOX genes plays a crucial role in the leukemogenesis and in many solid tumors mainly by means, the regulation of cell proliferation, cell death, metastasis and DNA repair. Keywords: HOX; Cancer; Hematopoiesis HOX GenesThe homeobox genes are a transcription factor family; they are divided in several classes. Class I homeobox genes (HOX in mice and HOX in humans), are 39 transcription factors, mainly involved in the regulation of embryonic development program; The HOX genes are characterized by a sequence of 183 nucleotides encoding a homeodomain of 61 amino acid that binds to DNA, as a biological gripper, activating or repressing specific genes [1,2].The HOX genes are organized into four chromosomal clusters or loci (HOXA Chr 7p15.3, HOXB Chr 17q21.3, HOXC Chr 12q13.3 and HOXD Chr 2q31), each having 9-11 genes.Based on the sequence similarity and their position into the locus, the corresponding genes, of the four clusters, can be aligned with each other in 13 paralogous groups (Figure 1) [3]. HOX gene expression controls the identity of several regions along the body axis according to the rules of temporal and spatial colinearity, with 3' HOX genes (retinoic acid responsive) expressed early in development and controlling anterior regions, followed by progressively more 5' genes (Fibroblast Growth Factor responsive) expressed later and controlling more posterior regions [4,5]. The HOX gene network, the most repeat-poor regions of the human genome [6], is also expressed in normal adult human organs [7]. Homeobox and HOX genes appear to regulate normal development, phenotype cell identity [8,9] cell differentiation [10,11] and control primary cellular processes, as proven by the description of congenital [12], somatic [13], metabolic [14] and neoplastic alterations [15,16] involving these genes. In addition to their role as transcriptional regulators, new crucial functions have recently been ascribed to HOX genes and homeoproteins mostly related to their interaction with miRNAs and ncRNAs to guarantee transcription and translation of specific RNA transcripts [17,18].The HOX network is active in adult human tissues and organs, controls the spatial-temporal generation of biological structure expected during embryonic development and regulates the cell memory program [4].

HOX Genes and Oncogenesis

“…HOX gene expression controls the identity of several regions along the body axis according to the rules of temporal and spatial colinearity, with 3' HOX genes (retinoic acid responsive) expressed early in development and controlling anterior regions, followed by progressively more 5' genes (Fibroblast Growth Factor responsive) expressed later and controlling more posterior regions [4,5]. The HOX gene network, the most repeat-poor regions of the human genome [6], is also expressed in normal adult human organs [7].…”