Work

Integrated analysis of single-cell and bulk RNA sequencing identifies APOC1 as a biomarker and therapeutic target for G0/G1 cell cycle arrest in cholangiocarcinoma

Year: 2025

Type: article

Abstract: Cholangiocarcinoma is characterized by its high malignancy, frequent recurrence and insensitivity to conventional radiotherapy and chemotherapy. This resistance may be associated with the presence of cells in the G0/G1 arrest phase within the cancer. Cancer cells in the G0/G1 phase are resistant to therapies targeting actively dividing cells, allowing them to evade conventional adjuvant treatments and survive. When conditions become favorable, these quiescent cells can re-enter the cell cycle, proliferate and potentially contribute to cancer recurrence. However, the biomarkers for identifying cells in the G0/G1 arrest phase within cholangiocarcinoma and the molecular mechanisms inducing G0/G1 arrest remain unclear. In our study, we first identified APOC1 as a characteristic gene for G0/G1 phase arrest in cholangiocarcinoma through bulk RNA sequencing (bulkRNA-seq). We then used single-cell RNA sequencing(scRNA-seq) for cell cycle inference and localized the expression peaks of APOC1 to verify its active cell cycle phase. Our experiments demonstrated that APOC1 can induce G0/G1 phase arrest in cholangiocarcinoma cells by inhibiting the Wnt/β-catenin signaling pathway, thereby suppressing cell proliferation, migration and invasion. This suggests that APOC1 may serve as a key regulatory factor and an important biomarker for cells in the G0/G1 phase of cholangiocarcinoma. • Distinct from the external effects of bioactive compounds and drugs, our study explores the molecular characteristics of G0/G1 phase arrest in cholangiocarcinoma, • We utilized scRNA-seq and bulkRNA-seq to investigate the temporal expression pattern of the APOC1 gene throughout the cell cycle in detail. • The mechanism of action of APOC1 was validated through in vivo and in vitro experiments.

Source: Genomics

DOI: 10.1016/j.ygeno.2025.111028