Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Graduate School, Nanjing, Jiangsu Province, 210008, China.
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, 210008, China.
J Exp Clin Cancer Res. 2024 May 6;43(1):136. doi: 10.1186/s13046-024-03055-2.
Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to lack of effective clinical interference. 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.
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.
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 yielded opposite effects. Mechanistically, DCAF1 could activate the Akt signaling pathway by binding to PARD3 and enhancing its expression. We also found that the combined application of DCAF1 knockdown and Akt inhibitor could significantly suppress subcutaneous xenograft tumor growth.
Our study illustrates that DCAF1 plays a crucial role in HCC development and the DCAF1/PARD3/Akt axis presents a potentially effective therapeutic strategy for HCC.
肝细胞癌（HCC）是一种预后不良的致命恶性肿瘤，缺乏有效的临床干预。DCAF1 在调节细胞生长和增殖方面发挥着重要作用，并且参与了各种恶性肿瘤的进展。然而，DCAF1 在 HCC 发展中的作用及其潜在机制尚不清楚。本研究旨在探讨 DCAF1 在 HCC 中的作用及其相应的分子机制。
采用定量实时 PCR、Western blot 和免疫组化检测肿瘤组织和细胞系中 DCAF1 的表达。随后，进行体外和体内实验探讨 DCAF1 在 HCC 肿瘤生长和转移中的作用。通过免疫共沉淀、质谱分析和 RNA 测序鉴定潜在的分子机制。
在这项研究中，我们发现 DCAF1 在 HCC 中明显上调，并与不良预后相关。DCAF1 敲低抑制肿瘤增殖和转移，促进肿瘤细胞凋亡，而过表达 DCAF1 则产生相反的效果。机制上，DCAF1 可以通过与 PARD3 结合并增强其表达来激活 Akt 信号通路。我们还发现，DCAF1 敲低联合 Akt 抑制剂可显著抑制皮下异种移植肿瘤的生长。
本研究表明，DCAF1 在 HCC 的发展中起着关键作用，DCAF1/PARD3/Akt 轴为 HCC 提供了一种潜在有效的治疗策略。
