ArticleBMC cancer2024
RPS6KA1 is a histone acetylation-related oncoprotein in acute myeloid leukemia which is targeted by afzelin.
Article in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Integrative phosphoproteomic network analysis identifies CAMK2D as a shared regulator of TPD52 family proteins in cancer.Protoplasma · 2026Article
- A novel anoikis resistance-associated gene model for prognostic prediction and immune microenvironment characterization in lung squamous cell carcinoma.Discover oncology · 2026Article
- Integration of single-cell sequencing, transcriptome sequencing, and machine learning for constructing and validating histone acetylation-related prognostic risk models in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Multi-omics analysis of the anti-cancer effects of curcumol in endometrial carcinoma.Frontiers in pharmacology · 2025Article
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Authors and funding
7 authors.
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Abstract
backgroundHistone acetylation plays a critical role in the progression of acute myeloid leukemia (AML). This study aimed to explore the prognostic significance and biological implications of histone acetylation-related genes in AML and to identify potential oncoproteins and therapeutic compounds.
methodsGenes associated with AML and histone acetylation were identified using the TCGA-LAML and IMEx Interactome databases. A histone acetylation-related risk model was developed using the least absolute shrinkage and selection operator method. The prognostic value of the model was evaluated through Kaplan-Meier survival analysis, time-dependent receiver operating characteristic curve, univariate and multivariate Cox regression, and nomogram calibration. Key genes were identified using random forest, support vector machine, and multivariate Cox analysis. Molecular docking was employed to assess the binding affinity between ribosomal protein S6 kinase A1 (RPS6KA1) and potential compounds. Furthermore, the effects of RPS6KA1 and afzelin on the malignant behaviors and downstream pathways of AML cells were validated through in vitro experiments.
resultsA risk model composed of 6 genes, including HDAC6, CREB3, KLF13, GOLGA2, RPS6KA1 and ZMIZ2, was established, demonstrating strong prognostic predictive capability. Among these, RPS6KA1 emerged as a key risk factor linked to histone acetylation status in AML. Elevated RPS6KA1 expression was observed in AML samples and was associated with poor prognosis. RPS6KA1 knockdown suppressed AML cell proliferation, migration, and invasion, induced G0/G1 phase arrest, and promoted apoptosis. Additionally, RPS6KA1 was identified as a potential target for afzelin, which exhibited anti-AML activity by inactivating RPS6KA1.
conclusionHistone acetylation status is closely associated with AML patient prognosis. RPS6KA1 acts as an oncoprotein in AML, facilitating disease progression. Afzelin may represent a novel therapeutic agent for AML by targeting RPS6KA1, which requires validation by clinical trials.
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