EP300 promotes hepatocellular carcinoma proliferation, migration and in vivo tumorigenicity revealed by integrated experimental and bioinformatic analyses.
1/5 보강
[BACKGROUND] Hepatocellular carcinoma (HCC) remains a lethal malignancy with high heterogeneity and limited effective biomarkers for risk stratification.
- HR 1.43
APA
Liu Z, Wang J, et al. (2026). EP300 promotes hepatocellular carcinoma proliferation, migration and in vivo tumorigenicity revealed by integrated experimental and bioinformatic analyses.. Journal of translational medicine, 24(1). https://doi.org/10.1186/s12967-026-07768-0
MLA
Liu Z, et al.. "EP300 promotes hepatocellular carcinoma proliferation, migration and in vivo tumorigenicity revealed by integrated experimental and bioinformatic analyses.." Journal of translational medicine, vol. 24, no. 1, 2026.
PMID
41639884
Abstract
[BACKGROUND] Hepatocellular carcinoma (HCC) remains a lethal malignancy with high heterogeneity and limited effective biomarkers for risk stratification. EP300 (p300), a central histone acetyltransferase and transcriptional co-activator, is frequently dysregulated in cancer, yet its integrated multi-omic and functional roles in HCC require further clarification.
[METHODS] We integrated transcriptomic and clinical data from TCGA-LIHC, proteomic data from CPTAC, and public survival resources, and validated EP300 expression in ten paired HCC tumors and adjacent tissues by RT-qPCR and western blotting. EP300 was silenced by siRNA in Huh-7 and SK-hep-1 cells followed by CCK-8, colony formation, wound-healing, and Transwell assays. Tumorigenicity was evaluated using a subcutaneous xenograft model. Immune associations were explored using established deconvolution algorithms.
[RESULTS] EP300 was significantly upregulated in HCC at both the mRNA level (TCGA unpaired: = 2.3 × 10; paired: = 2.2 × 10) and the protein level (CPTAC, = 165 tumors vs 165 normals: = 6.7006 × 10), and was higher in clinically high-risk strata (AFP > 400 ng/mL: = 0.01; stage III–IV vs I–II: = 0.04). High EP300 expression was associated with inferior overall survival in Kaplan–Meier analysis (HR = 1.43, 95% < 0.05), while the association was attenuated after adjustment for key clinical covariates (multivariable Cox: = 0.511). Functionally, EP300 knockdown reduced proliferation and clonogenicity ( < 0.0001) and impaired migration/invasion, and suppressed xenograft tumor growth. EP300 expression also correlated with an immunosuppressive tumor microenvironment signature in bulk RNA-seq analyses.
[CONCLUSION] EP300 is consistently upregulated in HCC and supports malignant phenotypes in vitro and in vivo. Its prognostic signal appears context-dependent after multivariable adjustment, suggesting EP300 is better interpreted as a progression-associated marker and potential therapeutic vulnerability. Immune-microenvironment associations derived from bulk data are hypothesis-generating and warrant orthogonal validation.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12967-026-07768-0.
[METHODS] We integrated transcriptomic and clinical data from TCGA-LIHC, proteomic data from CPTAC, and public survival resources, and validated EP300 expression in ten paired HCC tumors and adjacent tissues by RT-qPCR and western blotting. EP300 was silenced by siRNA in Huh-7 and SK-hep-1 cells followed by CCK-8, colony formation, wound-healing, and Transwell assays. Tumorigenicity was evaluated using a subcutaneous xenograft model. Immune associations were explored using established deconvolution algorithms.
[RESULTS] EP300 was significantly upregulated in HCC at both the mRNA level (TCGA unpaired: = 2.3 × 10; paired: = 2.2 × 10) and the protein level (CPTAC, = 165 tumors vs 165 normals: = 6.7006 × 10), and was higher in clinically high-risk strata (AFP > 400 ng/mL: = 0.01; stage III–IV vs I–II: = 0.04). High EP300 expression was associated with inferior overall survival in Kaplan–Meier analysis (HR = 1.43, 95% < 0.05), while the association was attenuated after adjustment for key clinical covariates (multivariable Cox: = 0.511). Functionally, EP300 knockdown reduced proliferation and clonogenicity ( < 0.0001) and impaired migration/invasion, and suppressed xenograft tumor growth. EP300 expression also correlated with an immunosuppressive tumor microenvironment signature in bulk RNA-seq analyses.
[CONCLUSION] EP300 is consistently upregulated in HCC and supports malignant phenotypes in vitro and in vivo. Its prognostic signal appears context-dependent after multivariable adjustment, suggesting EP300 is better interpreted as a progression-associated marker and potential therapeutic vulnerability. Immune-microenvironment associations derived from bulk data are hypothesis-generating and warrant orthogonal validation.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12967-026-07768-0.
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