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Deciphering HIC1 control pathways to reveal new avenues in cancer therapeutics

机译：解读HIC1控制途径以揭示癌症治疗方法的新途径

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Introduction: The tumor suppressor gene HIC1 (Hypermethylated in Cancer 1), which encodes a transcriptional repressor with multiple partners and multiple targets, is epigenetically silenced but not mutated in tumors. HIC1 has broad biological roles during normal development and is implicated in many canonical processes of cancer such as control of cell growth, cell survival upon genotoxic stress, cell migration, and motility. Areas covered: The HIC1 literature herein discussed includes its discovery as a candidate tumor suppressor gene hypermethylated or deleted in many human tumors, animal models establishing it as tumor suppressor gene, its role as a sequence-specific transcriptional repressor recruiting several chromatin regulatory complexes, its cognate target genes, and its functional roles in normal tissues. Finally, this review discusses how its loss of function contributes to the early steps in tumorigenesis. Expert opinion: Given HIC1's ability to direct repressive complexes to sequence-specific binding sites associated with its target genes, its loss results in specific changes in the transcriptional program of the cell. An understanding of this program through identification of HIC1's target genes and their involvement in feedback loops and cell process regulation will yield the ability to leverage this knowledge for therapeutic translation.
机译：简介：肿瘤抑制基因HIC1（在癌症1中为高甲基化）编码具有多个伙伴和多个靶标的转录阻遏物，在表观遗传上是沉默的，但不会在肿瘤中突变。 HIC1在正常发育过程中具有广泛的生物学作用，并且与癌症的许多规范过程有关，例如控制细胞生长，遗传毒性胁迫下的细胞存活，细胞迁移和运动。涵盖的领域：本文讨论的HIC1文献包括其在许多人类肿瘤中超甲基化或缺失的候选抑癌基因的发现，将其确立为抑癌基因的动物模型，其作为募集数种染色质调节复合物的序列特异性转录阻遏物的作用，相关靶基因及其在正常组织中的功能。最后，这篇综述讨论了其功能丧失如何促进肿瘤发生的早期步骤。专家意见：鉴于HIC1能够将阻抑复合物引导至与其靶基因相关的序列特异性结合位点，因此其丧失导致细胞转录程序发生特定变化。通过鉴定HIC1的靶基因及其在反馈环和细胞过程调控中的参与，对该程序的理解将产生利用该知识进行治疗性翻译的能力。

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