Work

ELOVL1 promotes the progression of intrahepatic cholangiocarcinoma by enhancing endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway

Year: 2026

Type: article

Abstract: BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy characterized by an adverse outcome attributed to delayed detection, elevated recurrence rates, and resistance to chemotherapy. Identifying innovative indicators and therapeutic targets is essential for enhancing iCCA treatment. METHODS: We used bioinformatics, machine learning, and experimental approaches to explore the role of ELOVL1 in iCCA. Functional enrichment analysis of DEGs was carried out utilizing GO, KEGG, GSEA, and GSVA. WGCNA and LASSO regression identified key genes linked to iCCA progression. In vitro and in vivo experiments assessed the impact of ELOVL1 on tumor growth, migration, invasion, and chemotherapy response. Western blotting and immunofluorescence were used to evaluate signaling pathways and ER stress markers. RESULTS: Bioinformatics analysis identified ELOVL1 as a key gene upregulated in iCCA tissues. High ELOVL1 expression correlated with poor prognosis. Functional assays showed that ELOVL1 overexpression enhanced iCCA cell proliferation, migration, invasion, and cisplatin resistance, while knockdown inhibited these effects. Mechanistically, ELOVL1 activated the PI3K/AKT/mTOR pathway and induced ER stress, promoting iCCA progression. Molecular docking studies identified ELOVL1's interaction with the PI3K inhibitor Pictilisib, suggesting a therapeutic target. CONCLUSION: ELOVL1 promotes iCCA progression by regulating the PI3K/AKT/mTOR pathway and enhancing ER stress. ELOVL1 is a potential biomarker for predicting iCCA prognosis and drug response, offering new therapeutic strategies for iCCA.

Source: Biology Direct

DOI: 10.1186/s13062-026-00790-8