You Song, Wang Fuqiang, Hu Qing, Li Pengtao, Zhang Changmao, Yu Yaqi, Zhang Yi, Li Qiu, Bao Qing, Liu Pingguo, Li Jie
Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma (Xiamen University Affiliated Zhongshan Hospital) Xiamen, Fujian, China.
Graduate College of Fujian Medical University Fuzhou, Fujian, China.
Am J Cancer Res. 2018 Oct 1;8(10):2076-2087. eCollection 2018.
YEATS domain containing 4 (YEATS4) is usually amplified and functions as an oncogene in several malignancies, such as colorectum, ovarian, breast and lung. However, the biological role of YEATS4 in hepatocellular carcinoma (HCC) has not yet been discussed. Herein, we found that YEATS4 was significantly upregulated in HCC compared to para-cancerous tissues, and was associated with poor prognosis, large tumor size, poor differentiation and distant metastasis. In addition, YEATS4 promoted HCC cell proliferation and colony formation by binding to and increasing the transcriptional activity of the TCEA1 promoter. Concurrently, upregulation of TCEA1 increased the stability of the DDX3 protein, a member of the DEAD box RNA helicase family, and augmented the proliferative and colony forming ability of HCC cells. Furthermore, YEATS4 accelerated tumor growth in a xenograft HCC model. Taken together, our study provides evidence for the first time on the potential role of the YEATS4/TCEA1/DDX3 axis in regulating HCC progression, and presents YEATS4 as a promising therapeutic target and prognosis maker for HCC.
含YEATS结构域蛋白4(YEATS4)在多种恶性肿瘤(如结直肠癌、卵巢癌、乳腺癌和肺癌)中通常会发生扩增并发挥癌基因的作用。然而,YEATS4在肝细胞癌(HCC)中的生物学作用尚未见报道。在此,我们发现与癌旁组织相比,YEATS4在HCC中显著上调,且与预后不良、肿瘤体积大、分化差及远处转移相关。此外,YEATS4通过结合并增加TCEA1启动子的转录活性来促进HCC细胞增殖和集落形成。同时,TCEA1的上调增加了DEAD盒RNA解旋酶家族成员DDX3蛋白的稳定性,并增强了HCC细胞的增殖和集落形成能力。此外,YEATS4在异种移植HCC模型中加速了肿瘤生长。综上所述,我们的研究首次为YEATS4/TCEA1/DDX3轴在调节HCC进展中的潜在作用提供了证据,并将YEATS4作为HCC一个有前景的治疗靶点和预后标志物。