Fan Weiwang, Ma Yuchen, Wu Jiaming, Zhang Xinchen
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, Heilongjiang, China.
Department of Cardiovascular Surgery, Central Hospital of Dalian University of Technology Dalian 116089, Liaoning, China.
Am J Cancer Res. 2025 Mar 15;15(3):1051-1065. doi: 10.62347/IAMC6442. eCollection 2025.
Nuclear casein kinase and cyclin-dependent kinases substrate 1 (NUCKS1) is overexpressed in hepatocellular carcinoma (HCC), but its role and regulatory mechanism in the development and progression of HCC remains unknown. Here, we report that the RNA and protein levels of NUCKS1 were significantly increased in HCC tissues. The inhibition of NUCKS1 notably decreased the proliferation and migration of SNU449 and HepG2 cells. However, NUCKS1 overexpression exacerbated cell growth and migration. Additionally, NUCKS1 depletion reduced the sphere formation efficiency and inhibited tumorigenesis in vivo. Mechanistically, depletion of NUCKS1 downregulated the expression of cell division control protein 42 (Cdc42), and NUCKS1 directly bound to the promoter of Cdc42 and transcriptionally upregulated Cdc42, which promoted the development and progression of HCC. Furthermore, the expression of NUCKS1 was positively associated with Cdc42 in HCC tissues. Collectively, our data indicate that the increasing expression of NUCKS1 plays an oncogenic role and promotes progression via transactivation of Cdc42 expression in HCC.
核酪蛋白激酶和细胞周期蛋白依赖性激酶底物1（NUCKS1）在肝细胞癌（HCC）中过表达，但其在HCC发生发展中的作用及调控机制尚不清楚。在此，我们报道NUCKS1的RNA和蛋白质水平在HCC组织中显著升高。抑制NUCKS1可显著降低SNU449和HepG2细胞的增殖和迁移。然而，NUCKS1过表达会加剧细胞生长和迁移。此外，NUCKS1缺失降低了球体形成效率并抑制了体内肿瘤发生。机制上，NUCKS1缺失下调了细胞分裂控制蛋白42（Cdc42）的表达，且NUCKS1直接与Cdc42的启动子结合并转录上调Cdc42，从而促进了HCC的发生发展。此外，在HCC组织中，NUCKS1的表达与Cdc42呈正相关。总体而言，我们的数据表明，NUCKS1表达增加在HCC中发挥致癌作用，并通过反式激活Cdc42表达促进进展。
