Transcriptional dysregulation induced by disease-defining genetic alterations of proteins in transcriptional machinery is a key feature of cancers. Mediator complex subunit 12 (MED12) is the central architectural subunit in the kinase module of Mediator, a large transcriptional regulatory complex that controls essential steps of transcription. Emerging evidence links deregulated MED12 to human cancers. MED12 is frequently mutated in benign tumors and cancers. Although the missense mutations of MED12 in benign tumors disrupt the kinase activity of Mediator, MED12 mutations in cancers could eliminate the interaction between Mediator complex and RNA polymerase II, leading to severe transcriptional misregulation. Aberrant expression of MED12 is associated with the prognosis of various types of human cancers. Loss of MED12 function has been associated with the development of resistance to chemotherapeutics. Moreover, MED12 is modified by posttranscriptional regulations. Arginine methylation of MED12 has been shown to regulate MED12-mediated transcriptional regulation and response to chemotherapeutics in human cancer cell lines. In this mini-review, the authors provide an overview of the roles of MED12 in the development of benign and malignant tumors as well as its roles in chemoresistance. The studies of MED12 exemplify that aberrant transcriptional programming is a therapeutic vulnerability for certain types of cancer.

中文翻译：

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介体复合物亚基12在肿瘤发生和对化学治疗反应中的新兴作用。

由疾病定义基因的转录机制中的蛋白质遗传改变引起的转录失调是癌症的关键特征。介体复合物亚基12（MED12）是介体激酶模块中的中心建筑亚基，介体是控制转录必不可少的大型转录调控复合体。新兴证据将解除管制的MED12与人类癌症联系起来。MED12在良性肿瘤和癌症中经常发生突变。尽管良性肿瘤中MED12的错义突变破坏了介体的激酶活性，但癌症中的MED12突变可以消除介体复合物与RNA聚合酶II之间的相互作用，从而导致严重的转录失调。MED12的异常表达与各种类型的人类癌症的预后相关。MED12功能的丧失与化学疗法耐药性的发展有关。此外，MED12被转录后法规修改。已显示MED12的精氨酸甲基化可调节人癌细胞系中的MED12介导的转录调控和对化学疗法的反应。在这份小型综述中，作者概述了MED12在良性和恶性肿瘤形成中的作用及其在化学耐药性中的作用。MED12的研究表明，异常的转录程序设计对某些类型的癌症具有治疗上的脆弱性。已显示MED12的精氨酸甲基化可调节人癌细胞系中的MED12介导的转录调控和对化学疗法的反应。在这份小型综述中，作者概述了MED12在良性和恶性肿瘤发展中的作用及其在化学耐药性中的作用。MED12的研究表明，异常的转录程序设计对某些类型的癌症具有治疗上的脆弱性。已显示MED12的精氨酸甲基化可调节人癌细胞系中的MED12介导的转录调控和对化学疗法的反应。在这份小型综述中，作者概述了MED12在良性和恶性肿瘤形成中的作用及其在化学耐药性中的作用。MED12的研究表明，异常的转录程序设计对某些类型的癌症具有治疗上的脆弱性。