Wang Ya-Tao, Yong Yu-Le, Liu Ze-Kun, Shen Yi-Xuan, Yang Xiang-Min, Chen Zhi-Nan
Department of Cell Biology, National Translational Science Center for Molecular Medicine, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
World J Gastrointest Oncol. 2025 Jun 15;17(6):106080. doi: 10.4251/wjgo.v17.i6.106080.
Hepatocellular carcinoma (HCC) ranks among the most prevalent and deadly malignancies, characterized by a high recurrence rate. Regulator of chromosome condensation 1 (RCC1) serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase (GTPase) and is implicated in various cancers. However, the role of RCC1 in HCC remains unexplored.
To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.
Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy. The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells. Furthermore, quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.
Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients. Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells, especially the proliferation of HCC cells, whereas RCC1 knockdown had the opposite effect. Mechanistically, we identified cell division cycle-associated (CDCA) 8 as a downstream target of RCC1 in HCC. RCC1 overexpression markedly increased CDCA8 levels, consequently enhancing cell proliferation and survival in HCC cells. Additionally, we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.
Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.
肝细胞癌（HCC）是最常见且致命的恶性肿瘤之一，其特点是复发率高。染色体凝聚调节因子1（RCC1）是一种主要的鸟嘌呤核苷酸交换因子，作用于与Ras相关的核蛋白鸟苷三磷酸酶（GTPase），并与多种癌症有关。然而，RCC1在HCC中的作用仍未得到探索。
阐明RCC1在HCC中的功能意义和分子机制。
运用生物信息学方法检测RCC1在HCC中的表达水平，并评估其对该恶性肿瘤预后的影响。采用细胞计数试剂盒-8法和流式细胞术评估HCC细胞的活力和细胞周期。此外，运用定量逆转录和免疫印迹法研究RCC1对细胞周期蛋白相关蛋白的影响。
生物信息学分析显示，RCC1在HCC中高表达，且与HCC患者的不良预后相关。功能研究表明，RCC1过表达促进了HCC细胞的恶性表型，尤其是HCC细胞的增殖，而RCC1基因敲低则产生相反的效果。机制上，我们确定细胞分裂周期相关蛋白8（CDCA8）是HCC中RCC1的下游靶点。RCC1过表达显著提高了CDCA8水平，从而增强了HCC细胞的增殖和存活能力。此外，我们发现RCC1通过CDCA8激活磷脂酰肌醇3激酶/蛋白激酶B/细胞周期蛋白依赖性激酶抑制剂1a通路，促进了HCC的发生和发展。
我们的研究为RCC1在HCC中的关键作用及其作为治疗靶点的潜力提供了深刻见解。
