Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 03100, Mexico.
Cells. 2021 Dec 28;11(1):75. doi: 10.3390/cells11010075.
A growing body of research on the transcriptome and cancer genome has demonstrated that many gynecological tumor-specific gene mutations are located in cis-regulatory elements. Through chromosomal looping, cis-regulatory elements interact which each other to control gene expression by bringing distant regulatory elements, such as enhancers and insulators, into close proximity with promoters. It is well known that chromatin connections may be disrupted in cancer cells, promoting transcriptional dysregulation and the expression of abnormal tumor suppressor genes and oncogenes. In this review, we examine the roles of alterations in 3D chromatin interactions. This includes changes in CTCF protein function, cancer-risk single nucleotide polymorphisms, viral integration, and hormonal response as part of the mechanisms that lead to the acquisition of enhancers or super-enhancers. The translocation of existing enhancers, as well as enhancer loss or acquisition of insulator elements that interact with gene promoters, is also revised. Remarkably, similar processes that modify 3D chromatin contacts in gene promoters may also influence the expression of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which have emerged as key regulators of gene expression in a variety of cancers, including gynecological malignancies.
越来越多的关于转录组和癌症基因组的研究表明，许多妇科肿瘤特异性基因突变位于顺式调控元件中。通过染色体环化，顺式调控元件相互作用，通过将远距离的调控元件（如增强子和绝缘子）与启动子拉近，来控制基因表达。众所周知，染色质连接可能在癌细胞中被破坏，促进转录失调和异常肿瘤抑制基因和癌基因的表达。在这篇综述中，我们研究了 3D 染色质相互作用改变的作用。这包括 CTCF 蛋白功能的改变、癌症风险单核苷酸多态性、病毒整合以及激素反应，这些都是导致获得增强子或超级增强子的机制的一部分。现有增强子的易位，以及与基因启动子相互作用的增强子缺失或获得绝缘子元件，也进行了修订。值得注意的是，在基因启动子中修饰 3D 染色质接触的类似过程也可能影响非编码 RNA 的表达，例如长非编码 RNA（lncRNA）和 microRNAs（miRNA），它们已成为多种癌症（包括妇科恶性肿瘤）中基因表达的关键调节剂。
