放射抵抗是肝癌放疗局部失败的主要原因，发生机制尚不明确。铜代谢相关蛋白COMMD10是我们通过酵母双杂交系统筛选并首次鉴定的抑癌基因。前期研究发现，COMMD10在放射抵抗的肝癌组织中呈显著低表达，在放射敏感的肝癌组织表达上调；敲低肝癌细胞株HepG2的COMMD10表达，诱导了HepG2的放射抵抗，并伴随缺氧诱导因子HIF-1的亚单位HIF-1α表达显著上调，后者是诱导肝癌放射抵抗的重要因子。因此，我们认为COMMD10可能通过HIF-1介导的信号通路调控肝癌放射敏感性，但其作用机制尚不清楚。本研究将从细胞、动物实验和临床三个层次，深入研究COMMD10对肝癌放射敏感性的影响，探索COMMD10与HIF-1的相互作用机制以及与肝癌放疗疗效的相关性，阐明COMMD10在肝癌辐射增敏的作用机制，为COMMD10成为新的放射敏感性预测指标、潜在放射增敏治疗靶点，开展肝癌精准放疗提供理论基础。

Radiation resistance is the major cause of the local failure for hepatocellular carcinoma(HCC), however, the underlying mechanism is not clear. Our previous study identified COpper Metabolism gene Murr1 Domain-10 (COMMD10), which was screened using a yeast two-hybrid system, as a suppressor gene in the pathogenesis of HCC. We found that the COMMD10 was down-expressed in the radioresistant cancer tissues in HCC patients, whereas it was over-expressed in the radiosensitive tissues. Along with the enhanced radioresistance in COMMD10-knockdown HepG2 cells, mRNA level of HIF-1α, known as a subunit of HIF-1, was observed significantly increased. It has been reported that HIF-1 pathway has a profound effect on the enhancement of radioresistance in HCC. Therefore, we hypothesize that COMMD10 regulates radiosensitivity of HCC via HIF-1 signaling pathway, though its mechanism is unclear yet. This study will explore the effects of COMMD10 on radiation sensitivity of HCC, the detailed interaction between COMMD10 and HIF-1, as well as the potential value of COMMD10 as a novel treatment target in HCC. The results of the study will provide an effective approach for the prediction of radiosensitivity as well as evaluation of prognosis, and explore a potential molecular target for radiosensitization. This work will help for developing and enriching the theory of precision radiotherapy of HCC.