Krivtsova Olga, Makarova Anna, Lazarevich Natalia
Federal State Budgetary Institution, "N. N. Blokhin Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation, Moscow 115478, Russian.
World J Hepatol. 2018 Oct 27;10(10):645-661. doi: 10.4254/wjh.v10.i10.645.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and the second leading cause of death among all cancer types. Deregulation of the networks of tissue-specific transcription factors (TFs) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression. In addition, recent reports suggest that substantial aberrations in the production of TF isoforms occur in HCC. experiments have identified distinct isoform-specific regulatory functions and related biological effects of liver-specific TFs that are implicated in carcinogenesis, which may be relevant for tumor progression and clinical outcome. This study reviews available data on the expression of isoforms of liver-specific and ubiquitous TFs in the liver and HCC and their effects, including HNF4α, C/EBPs, p73 and TCF7L2, and indicates that assessment of the ratio of isoforms and targeting specific TF variants may be beneficial for the prognosis and treatment of HCC.
肝细胞癌(HCC)是全球最常见的恶性肿瘤之一,也是所有癌症类型中第二大死亡原因。在HCC中观察到的组织特异性转录因子(TFs)网络失调导致肝脏转录程序发生深刻变化,从而促进肿瘤进展。此外,最近的报告表明,HCC中TF异构体的产生存在大量异常。实验已经确定了肝脏特异性TFs的不同异构体特异性调节功能和相关生物学效应,这些效应与致癌作用有关,可能与肿瘤进展和临床结果相关。本研究综述了关于肝脏特异性和普遍存在的TFs异构体在肝脏和HCC中的表达及其影响的数据,包括肝细胞核因子4α(HNF4α)、CCAAT增强子结合蛋白(C/EBPs)、p73和转录因子7样蛋白2(TCF7L2),并表明评估异构体比例和靶向特定TF变体可能对HCC的预后和治疗有益。