Feng Senwen, Liu Junhao, Hailiang Li, Wen Jianfan, Zhao Yujun, Li Xiaofeng, Lu Guankun, Gao Peng, Zeng Xiancheng
Department of General Surgery, Guangdong Second Provincial General Hospital, 466 Xingang Middle Road, Haizhu District, Guangzhou 510317, China.
Transl Oncol. 2021 Aug;14(8):101124. doi: 10.1016/j.tranon.2021.101124. Epub 2021 May 25.
Liver cancer was reported to be the sixth most frequently diagnosed cancer, and hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancer. Nevertheless, the concrete molecular mechanisms of HCC progression remain obscure, which is essential to elucidate. The expression profile of RAD54B in HCC was measured using qPCR and western blotting. Moreover, the levels of RAD54B in paraffin-embedded samples were evaluated using immunohistochemistry (IHC). The effect of RAD54B on HCC progression was testified by in vitro experiments, and in vivo orthotopic xenograft tumor experiments. The mechanisms of RAD54B promoting HCC progression were investigated through molecular and function experiments. Herein, RAD54B are dramatically upregulated in HCC tissues and cell lines both on mRNA and protein levels, and RAD54B can servers as an independent prognostic parameter of 5-year overall survival and 5-year disease-free survival for patients with HCC. Moreover, up-regulation of RAD54B dramatically increases the capacity for in vitro cell viability and motility, and in vivo intrahepatic metastasis of HCC cells. Mechanistically, RAD54B promotes the HCC progression through modulating the wnt/β-catenin signaling. Notably, blocking the wnt/β-catenin signaling axis can counteract the activating effects of RAD54B on motility of HCC cells. Besides, further analysis illustrates that DNA amplification is one of the mechanisms leading to mRNA overexpression of RAD54B in HCC. Our findings indicate that RAD54B might be a promising potential prognostic marker and a candidate therapeutic target to therapy HCC.
据报道，肝癌是第六大最常被诊断出的癌症，肝细胞癌（HCC）占原发性肝癌的75%-85%。然而，HCC进展的具体分子机制仍不清楚，而阐明这些机制至关重要。使用qPCR和蛋白质印迹法检测了HCC中RAD54B的表达谱。此外，使用免疫组织化学（IHC）评估了石蜡包埋样本中RAD54B的水平。通过体外实验和体内原位异种移植肿瘤实验证实了RAD54B对HCC进展的影响。通过分子和功能实验研究了RAD54B促进HCC进展的机制。在此，RAD54B在HCC组织和细胞系中的mRNA和蛋白质水平均显著上调，并且RAD54B可作为HCC患者5年总生存率和5年无病生存率的独立预后参数。此外，RAD54B的上调显著增加了体外细胞活力和运动能力以及HCC细胞在体内的肝内转移能力。机制上，RAD54B通过调节Wnt/β-连环蛋白信号促进HCC进展。值得注意的是，阻断Wnt/β-连环蛋白信号轴可抵消RAD54B对HCC细胞运动的激活作用。此外，进一步分析表明DNA扩增是导致HCC中RAD54B mRNA过表达的机制之一。我们的研究结果表明，RAD54B可能是一个有前景的潜在预后标志物和治疗HCC的候选治疗靶点。
