Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.
Biochem Biophys Res Commun. 2010 Apr 9;394(3):623-7. doi: 10.1016/j.bbrc.2010.03.036. Epub 2010 Mar 10.
Hepatocellular carcinoma (HCC) is a malignant form of liver cancer that ranks the second leading cause of cancer-related deaths in China and many Asia regions. The dismal outcome reflects the need for a better understanding of the transcriptional control of oncogenic signaling pathway. Our recent findings have identified yes-associated protein (YAP) is a potent oncogenic driver and independent prognostic risk factor of HCC. The present study aims to elucidate the transcriptional regulation of YAP targeted by microRNA (miRNA). miR-375 is a putative target and was found significantly down-regulated in the tumor versus adjacent non-tumor tissues of HCC patients (n=48). As determined by luciferase reporter assay, we found ectopic expression of miR-375 could diminish the transcriptional activity of YAP. Furthermore, immunoblotting revealed miR-375 suppressed endogenous YAP protein level. Functional assays showed that miR-375 was able to inhibit proliferation and invasion of HCC cells.
miR-375 is an important regulator of YAP oncogene, implicating a potential therapeutic role in HCC treatment.
肝细胞癌（HCC）是一种恶性肝癌，在中国和许多亚洲地区排名癌症相关死亡的第二大原因。这种惨淡的结果反映了需要更好地了解致癌信号通路的转录控制。我们最近的研究结果表明，Yes 相关蛋白（YAP）是 HCC 的一个强大致癌驱动因子和独立预后风险因素。本研究旨在阐明 microRNA（miRNA）靶向 YAP 的转录调控。miR-375 是一个假定的靶点，在 HCC 患者的肿瘤与相邻非肿瘤组织（n=48）中发现其表达显著下调。通过荧光素酶报告基因检测，我们发现外源性表达 miR-375 可降低 YAP 的转录活性。此外，免疫印迹显示 miR-375 抑制内源性 YAP 蛋白水平。功能测定表明，miR-375 能够抑制 HCC 细胞的增殖和侵袭。
miR-375 是 YAP 致癌基因的重要调节因子，暗示其在 HCC 治疗中具有潜在的治疗作用。
