Jia Yunlong, Bleicher Françoise, Merabet Samir
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, Lyon, France.
Int J Dev Biol. 2018;62(11-12):865-876. doi: 10.1387/ijdb.180286fb.
HOX and TALE genes encode homeodomain (HD)-containing transcription factors that act in concert in different tissues to coordinate cell fates and morphogenesis throughout embryonic development. These two evolutionary conserved families contain several members that form different types of protein complexes on DNA. Mutations affecting the expression of HOX or TALE genes have been reported in a number of cancers, but whether and how the two gene families could be perturbed together has never been explored systematically. As a consequence, the putative collaborative role between HOX and TALE members for promoting or inhibiting oncogenesis remains to be established in most cancer contexts. Here, we address this issue by considering HOX and TALE expression profiling in normal and cancer adult tissues, using normalized RNA-sequencing expression data deriving from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) research projects. Information was extracted from 28 cancer types originating from 21 different tissues, constituting a unique comparative analysis of HOX and TALE expression profiles between normal and cancer contexts in human. We present the general and specific rules that could be deduced from this large-scale comparative analysis. Overall this work provides a precious annotated support to better understand the role of specific HOX/TALE combinatorial codes in human cancers.
HOX基因和TALE基因编码含同源结构域(HD)的转录因子,这些转录因子在不同组织中协同作用,在整个胚胎发育过程中协调细胞命运和形态发生。这两个进化上保守的基因家族包含多个成员,它们在DNA上形成不同类型的蛋白质复合物。已有报道称,多种癌症中存在影响HOX基因或TALE基因表达的突变,但这两个基因家族是否以及如何共同受到干扰,从未得到系统研究。因此,在大多数癌症背景下,HOX基因和TALE基因成员在促进或抑制肿瘤发生方面的假定协同作用仍有待确定。在此,我们通过利用来自癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)研究项目的标准化RNA测序表达数据,分析正常和癌症成人组织中的HOX基因和TALE基因表达谱,来解决这一问题。我们从源自21种不同组织的28种癌症类型中提取信息,对人类正常和癌症背景下的HOX基因和TALE基因表达谱进行了独特的比较分析。我们展示了可以从这项大规模比较分析中推断出的一般规则和特定规则。总体而言,这项工作为更好地理解特定HOX/TALE组合编码在人类癌症中的作用提供了宝贵的注释支持。