Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma.
Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma.
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DOI：
10.1016/j.livres.2017.08.005
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Zhong S
中科院分区：
文献类型：
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作者：
Lei J;Chen S;Zhong S
RNA 聚合酶 III 依赖性基因（Pol III 基因）的产物（包括 tRNA 和 5S rRNA）的水平在转化细胞和肿瘤细胞中升高，从而增强肿瘤发生。 TFIIB 相关因子 1 (Brf1) 是一种关键转录因子，特异性调节 Pol III 基因的转录。体内和体外研究表明，Brf1 的减少会减少 Pol III 基因转录，足以抑制细胞转化和肿瘤形成。新的证据表明，Brf1 和 Pol III 基因的失调与人类和动物肝细胞癌 (HCC) 的发展有关。我们报道了 Brf1 在人类肝癌患者中过度表达，并且 Brf1 水平高的患者生存期较短。本综述总结了这些基因失调对 HCC 的影响及其通过信号通路和表观遗传学的调节。这些新数据应该有助于我们从不同的角度确定HCC的分子机制，并指导HCC患者治疗方法的开发。
The levels of the products of RNA polymerase III-dependent genes (Pol III genes), including tRNAs and 5S rRNA, are elevated in transformed and tumor cells, which potentiate tumorigenesis. TFIIB-related factor 1 (Brf1) is a key transcription factor and specifically regulates the transcription of Pol III genes. In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces Pol III gene transcription and is sufficient for inhibiting cell transformation and tumor formation. Emerging evidence indicates that dysregulation of Brf1 and Pol III genes is linked to the development of hepatocellular carcinoma (HCC) in humans and animals. We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals. This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics. These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.