Transcriptomic Analysis Reveals the Role of in Hepatocellular Carcinoma and Its Association With the Wnt/-catenin Signaling Pathway.

[BACKGROUND] Hepatocellular carcinoma (HCC) shows high incidence and mortality worldwide. , an E3 ubiquitin ligase within the TRIM family, exerts regulatory functions in various tumors. This study analyzed the expression patterns and potential functions of in HCC based on transcriptomic data.

[METHODS] First, the differential expression of TRIM26 between tumor and normal tissues was analyzed using the TCGA dataset and cross-validated using TIMER 2.0 and HCCDB. Enrichment analysis evaluated its association with hallmark pathways including Wnt/-catenin. A gene functional interaction network was built via GeneMANIA to explore TRIM26 and the Wnt/-catenin pathway. Immune cell infiltration was quantified by ssGSEA for immune microenvironment correlation. scRNA-seq data established an HCC single-cell atlas to define TRIM26 distribution across cell subsets. AUCell was used to assess TRIM26-pathway associations within specific cell types.

[RESULTS] TRIM26 was significantly upregulated in HCC tissues, and its high expression correlated with enrichment of oncogenic pathways including Wnt/-catenin, G2/M checkpoint, and TGF-. GeneMANIA showed that TRIM26 interacted directly or indirectly with Wnt/-catenin core molecules, implying its regulatory role. TRIM26 expression was closely linked to infiltration of activated B cells, CD8 T cells, and NKT cells. Single-cell analysis revealed TRIM26 was mainly expressed in hepatocytes, T/NK cells, myeloid cells, and B cells. Importantly, in hepatocytes, TRIM26 strongly correlated with Wnt/-catenin activity, which was much higher in tumor hepatocytes than normal ones.

[CONCLUSION] In HCC, TRIM26 was abnormally overexpressed. TRIM26 may regulate tumor progression via the Wnt/-catenin pathway and is linked to immune infiltration. Thus, TRIM26 is a potential therapeutic target for HCC.