RCC1 promotes hepatocellular carcinoma proliferation via CDCA8-dependent activation of PI3K/Akt signaling

Hepatocellular carcinoma (HCC) ranks among the most prevalent and deadly malignancies, characterized by a high recurrence rate. Regulator of Chromo-some Condensation 1 (RCC1) serves as a principal guanine nucleotide exchange factor for Ran GTPase and is implicated in various cancers. However, the role of RCC1 in HCC remains unexplored. In this study, bioinformatics analysis revealed that RCC1 is highly expressed in HCC and correlates with poor prognosis in HCC patients. Functional studies showed that RCC1 overexpression promoted the proliferation and G1/S phase transition of HCC cells, whereas RCC1 knockdown had the opposite effect. Mechanistically, we identified CDCA8 as a downstream target of RCC1 in HCC. RCC1 overexpression markedly increases CDCA8 levels, consequently enhancing cell proliferation and survival in HCC cells. Additionally, we discovered that RCC1 contributes to the development and progression of HCC by activating the PI3K/Akt/p21 pathway through CDCA8. Collectively, our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.