Video Experimental Relacionado

Updated: Jan 29, 2026

Assays for Validating Histone Acetyltransferase Inhibitors

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Modulación transcripcional diferencial por el inhibidor de histona deacetilasa SAHA en LUAD y LUSC

Fei Wang¹, Qingjun Yang¹, Lei Shu¹

¹The Affiliated Panyu Central Hospital, Guangzhou Women and Children's Medical Center, Infection Medicine Research Institute of Panyu District, School of Biomedical Engineering, Guangdong University of Technology, The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.

Clinical epigenetics

|January 28, 2026

Resumen

Los inhibidores de histona deacetilasa (HDACi) como SAHA muestran respuestas variables en subtipos de cáncer de pulmón no microcítico (CPNM). SAHA activa distintos módulos genéticos específicos de linaje en adenocarcinoma de pulmón (LUAD) y carcinoma escamoso de pulmón (LUSC), ofreciendo estrategias terapéuticas adaptadas a cada subtipo.

Área de la Ciencia:

Epigenetics; Cancer Biology; Pharmacogenomics

Sus antecedentes:

Histone deacetylases (HDACs) are key epigenetic regulators in non-small cell lung cancer (NSCLC).; Responses to HDAC inhibitors (HDACi) differ significantly between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC).

Objetivo del estudio:

To investigate how suberoylanilide hydroxamic acid (SAHA, vorinostat), a pan-HDAC inhibitor, alters lineage-specific transcriptional programs in LUAD and LUSC.; To determine if SAHA-aligned gene modules, not individual genes, reveal clinically relevant vulnerabilities in each NSCLC subtype.

Principales métodos:

Utilized bulk RNA-sequencing on LUAD-like (NCI-H1299) and LUSC-like (NCI-H1703) cells treated with SAHA or DMSO.; Performed differential gene expression analysis, gene ontology (GO)/Reactome over-representation, Hallmark Gene Set Enrichment Analysis (GSEA), and protein-protein interaction mapping.; Constructed SAHA "feature-sensing" modules by intersecting SAHA-responsive differentially expressed genes (DEGs) with overall-survival-associated genes, and analyzed these modules in TCGA LUAD and LUSC tumor cohorts.

Principales resultados:

SAHA modulated transcriptomes in both cell lines, inducing shared suppression of cell-cycle programs (E2F/G2-M) but diverging in other outputs.; In LUAD-like cells, SAHA upregulated morphogenesis/adhesion and KRAS signaling, while dampening interferon/stress pathways, and reduced migration.; In LUSC-like cells, SAHA triggered cell-cycle checkpoint shutdown, induced complement/ECM and inflammatory responses, increased apoptosis, and showed modest migration restraint. Four SAHA feature-sensing modules were identified, with LUAD_RISK and LUSC_RISK modules stratifying prognosis and linked to distinct HDAC isoform neighborhoods.

Conclusiones:

SAHA establishes a common anti-proliferative effect but activates distinct subtype-specific risk modules in LUAD (cell-cycle/migration-linked) and LUSC (checkpoint/stress-linked).; These SAHA feature-sensing modules offer a framework for developing subtype-tailored HDAC inhibitor combinations and biomarkers for NSCLC.

Palabras clave:

inhibidores de HDAC CPNM terapia personalizada SAHA modulación transcripcional

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