Huang Zeli, Su Bojin, Liu Fang, Zhang Ning, Ye Yilong, Zhang Yang, Zhen Zhenghe, Liang Shaoqiang, Liang Shaobo, Chen Lushi, Luo Weijun, Claret François X, Huang Ying, Xu Tao
Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan 528000, Guangdong Province, People's Republic of China.
Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People's Republic of China.
Onco Targets Ther. 2020 Jun 17;13:5629-5642. doi: 10.2147/OTT.S247699. eCollection 2020.
Nasopharyngeal carcinoma (NPC) patients with HBsAg (+) commonly present with high frequencies of distant metastasis and poor survival rate; however, the mechanism has not been elucidated.
We analyzed the yes-associated protein 1 (YAP1) expression between HBsAg (+) and HBsAg (-) of NPC patients, then analyzed the relationship of YAP1 with survival. We further explored the anti-tumor role in NPC cell lines using YAP1 siRNA technique, and checked whether YAP1 regulatesepithelial-mesenchymal transition ( EMT). The relationship between HBV X protein (HBx) and YAP1 was also tested using Dual-Luciferase reporter assay. Finally, we explored anti-YAP1 to inhibit tumor metastasis using the xenograft mice model.
In the current study, we found that YAP1 expression was higher in HBsAg (+) samples than in the HBsAg (-) samples, as a clinical signature, suggesting that YAP1 could be used as a prognostic factor for NPC. Our results showed that the HBx could regulate YAP1, further promoting cellular invasiveness through EMT. Anti-YAP1 can also decrease metastasis in vivo.
Our findings suggest that YAP1 is a promising prognostic factor in NPC and could be used as a potential treatment target for NPC with HBV infection.
乙肝表面抗原（HBsAg）阳性的鼻咽癌（NPC）患者通常远处转移频率高且生存率低；然而，其机制尚未阐明。
我们分析了NPC患者HBsAg阳性与阴性之间的Yes相关蛋白1（YAP1）表达，然后分析了YAP1与生存的关系。我们使用YAP1 siRNA技术进一步探讨其在NPC细胞系中的抗肿瘤作用，并检测YAP1是否调节上皮-间质转化（EMT）。还使用双荧光素酶报告基因检测法检测了乙肝病毒X蛋白（HBx）与YAP1之间的关系。最后，我们使用异种移植小鼠模型探索抗YAP1抑制肿瘤转移的作用。
在本研究中，我们发现YAP1在HBsAg阳性样本中的表达高于HBsAg阴性样本，作为一种临床特征，表明YAP1可作为NPC的预后因素。我们的结果表明，HBx可调节YAP1，通过EMT进一步促进细胞侵袭性。抗YAP1也可在体内减少转移。
我们的研究结果表明，YAP1是NPC中有前景的预后因素，可作为HBV感染的NPC的潜在治疗靶点。
