POTEF upregulation drives hepatocellular carcinoma progression via oncogenic signaling and immune modulation

Members of the POTE gene family have been implicated in tumorigenesis across multiple malignancies. However, the biological and clinical significance of POTEF in hepatocellular carcinoma (HCC) remains unclear. Differential expression analyses of POTE family genes were performed using transcriptomic sequencing of 12 paired HCC and adjacent tissues and validated using TCGA and GEO datasets. POTEF expression was further confirmed by qRT-PCR, western blotting, and immunohistochemistry in clinical specimens. Functional assays, including CCK-8, wound-healing, apoptosis, and xenograft experiments, were conducted following POTEF overexpression or silencing in Huh7 cells. Transcriptomic analyses, pathway enrichment, and immune infiltration analyses were subsequently performed. POTEF was significantly upregulated in HCC tissues and was associated with unfavorable prognosis, advanced pathological stage, vascular invasion, and elevated serum AFP levels. Functional assays demonstrated that POTEF promoted hepatocellular carcinoma cell proliferation and migration while suppressing apoptosis in vitro, and xenograft experiments further showed that POTEF enhanced tumor growth in vivo.Transcriptomic profiling revealed enrichment of pathways related to extracellular matrix remodeling and carcinogenesis-associated signaling. Further experimental analyses suggested that POTEF may contribute to HCC progression partly through epithelial-mesenchymal transition-associated regulation. In addition, POTEF expression was positively associated with macrophage infiltration, particularly CD163-positive macrophage enrichment. Collectively, these findings indicate that POTEF is significantly upregulated in hepatocellular carcinoma and is associated with EMT-related regulation and macrophage infiltration, highlighting its potential clinical relevance as a diagnostic and prognostic biomarker.