背景：肝细胞癌（Hepatocellular carcinoma, HCC）是一种致命性的恶性肿瘤，由于 现 有 的 临 床 干 预 措 施 疗 效 有 限 ， 其 预 后 较 差 。 DDB1-CUL4 相 关 因 子 1 （DDB1-CUL4-associated factor 1, DCAF1）在调节细胞生长和增殖中起着至关重要 的作用，并参与调控多种恶性肿瘤的进展。然而，DCAF1 在肝细胞癌进展中的功 能及其作用机制尚未被阐明。本研究旨在探讨 DCAF1 在肝细胞癌进展中所发挥的 作用及其分子机制。 方法：采用实时荧光定量 PCR、Western blot 和免疫组化染色检测 DCAF1 在肿瘤组 织和细胞系中的表达。随后，通过体外和体内实验研究 DCAF1 在肝细胞癌生长和 转移中所发挥的作用。通过免疫共沉淀、质谱分析和 RNA 测序进一步研究 DCAF1 调控肝细胞癌进展的分子机制。通过构建皮下瘤模型检测敲低 DCAF1 与 Akt 抑制 剂联合应用对肿瘤生长的抑制作用。 结果：DCAF1 在肝细胞癌患者肿瘤组织中的表达量明显升高。在肝细胞癌患者中， DCAF1 表达水平与 T 分期及 AJCC 分期相关，且 DCAF1 高表达者的总体生存时间 更短。在肝细胞癌细胞系中敲低 DCAF1 抑制肿瘤细胞的增殖及转移、促进肿瘤细 胞凋亡，而过表达 DCAF1 促进肿瘤的增殖、转移，抑制肿瘤细胞调亡。从机制上 来看，DCAF1 可以通过结合 PARD3 并增强其表达，从而激活 Akt 信号通路。本研 究创新性地发现敲低 DCAF1 和 Akt 抑制剂联合应用可显著抑制裸鼠皮下瘤的生长。 结论：本研究表明 DCAF1 在肝细胞癌进展中起着至关重要的作用。DCAF1 高表达 与临床不良预后相关，DCAF1/PARD3/Akt 轴为肝细胞癌治疗提供了潜在新策略。

Background: Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to the limited efficacy of existing clinical interventions. DDB1-CUL4-associated factor 1 (DCAF1) plays a vital role in regulating cell growth and proliferation, and is involved in the progression of various malignancies. However, the function of DCAF1 in HCC development and the underlying mechanism are still unknown. This study aimed to explore the effect of DCAF1 in HCC and the corresponding molecular mechanism. Methods: Quantitative real-time PCR, Western blot and immunostaining were used to determine DCAF1 expression in tumor tissues and cell lines. Subsequently, in vitro and in vivo experiments were conducted to explore the function of DCAF1 in tumor growth and metastasis in HCC. Coimmunoprecipitation, mass spectrometry and RNA sequencing were performed to identify the underlying molecular mechanisms. Subcutaneous tumor model was conducted to test the inhibitive effect of combined use of DCAF1 knockdown and Akt inhibitor. Results: In this study, we found that DCAF1 was observably upregulated and associated with poor prognosis in HCC. Knockdown of DCAF1 inhibited tumor proliferation and metastasis and promoted tumor apoptosis, whereas overexpressing DCAF1 enhanced tumor proliferation and metastasis, and suppressed tumor apoptosis. Mechanistically, DCAF1 could activate the Akt signaling pathway by binding to PARD3 and enhancing its expression. The study innovatively found that the combined application of DCAF1 knockdown and Akt inhibitor could significantly suppress subcutaneous xenograft tumor growth. Conclusions: The study illustrates that DCAF1 plays a crucial role in HCC development. DCAF1 high expression is correlated with poor clinical prognosis, and the DCAF1/PARD3/Akt axis presents a potentially effective therapeutic strategy for HCC.