Bhatlekar Seema, Fields Jeremy Z, Boman Bruce M
Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute, Newark, DE, USA.
Department of Biological Sciences, University of Delaware, Newark, DE, USA.
Stem Cells Int. 2018 Jul 22;2018:3569493. doi: 10.1155/2018/3569493. eCollection 2018.
HOX genes encode an evolutionarily conserved set of transcription factors that control how the phenotype of an organism becomes organized during development based on its genetic makeup. For example, in bilaterian-type animals, HOX genes are organized in gene clusters that encode anatomic segment identity, that is, whether the embryo will form with bilateral symmetry with a head (anterior), tail (posterior), back (dorsal), and belly (ventral). Although HOX genes are known to regulate stem cell (SC) differentiation and HOX genes are dysregulated in cancer, the mechanisms by which dysregulation of HOX genes in SCs causes cancer development is not fully understood. Therefore, the purpose of this manuscript was (i) to review the role of HOX genes in SC differentiation, particularly in embryonic, adult tissue-specific, and induced pluripotent SC, and (ii) to investigate how dysregulated HOX genes in SCs are responsible for the development of colorectal cancer (CRC) and acute myeloid leukemia (AML). We analyzed HOX gene expression in CRC and AML using information from The Cancer Genome Atlas study. Finally, we reviewed the literature on HOX genes and related therapeutics that might help us understand ways to develop SC-specific therapies that target aberrant HOX gene expression that contributes to cancer development.
HOX基因编码一组进化上保守的转录因子，这些转录因子根据生物体的基因组成来控制其在发育过程中的表型形成方式。例如，在两侧对称型动物中，HOX基因以基因簇的形式排列，这些基因簇编码解剖学节段身份，也就是说，胚胎是否会形成具有头部（前部）、尾部（后部）、背部（背部）和腹部（腹部）的双侧对称。尽管已知HOX基因调节干细胞（SC）分化，并且HOX基因在癌症中失调，但干细胞中HOX基因失调导致癌症发展的机制尚未完全了解。因此，本手稿的目的是（i）综述HOX基因在SC分化中的作用，特别是在胚胎、成人组织特异性和诱导多能干细胞中的作用，以及（ii）研究干细胞中失调的HOX基因如何导致结直肠癌（CRC）和急性髓细胞白血病（AML）的发展。我们利用癌症基因组图谱研究的信息分析了CRC和AML中HOX基因的表达。最后，我们综述了关于HOX基因和相关治疗方法的文献，这些文献可能有助于我们理解开发针对异常HOX基因表达的SC特异性疗法的方法，而异常HOX基因表达会导致癌症发展。
