Evidence map›Paper›PMID 41593801›Full record

ArticleClinical epigenetics2026

Differential transcriptomic modulation by histone deacetylase inhibitor SAHA in LUAD and LUSC.

Fei Wang, Qingjun Yang, Lei Shu, Huiyu Cen, Yating Huang, Xiaojun Ma, Yinshan Lin, Xiaoling Guan, Chen Wang, Xihua Fu and 4 more

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Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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14 authors.

Fei Wang *The 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.
Qingjun Yang *The 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.
Lei Shu *The 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.
Huiyu Cen *The 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.
Yating HuangThe 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.
Xiaojun MaThe 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.
Yinshan LinThe 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.
Xiaoling GuanThe 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.
Chen WangThe 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.
Xihua FuThe 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.
Guoxing YouThe 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.
Xi-Yong YuThe 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. yuxycn@aliyun.com.
Lingmin ZhangThe 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. zhanglm@gzhmu.edu.cn.
Jianfen SuThe 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. suphen_so@163.com.

Funding

The National Natural Science Foundation of China 82070406, 82072047, and 82170008
6 · The paper itself

Abstract

backgroundHistone deacetylases (HDACs) are central epigenetic regulators in non-small cell lung cancer (NSCLC), yet responses to HDAC inhibitors (HDACi) vary markedly between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). We asked how the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) rewires lineage-specific transcriptional programs and whether SAHA-aligned modules of genes, rather than individual loci, capture clinically relevant vulnerabilities in each subtype.

methodsLUAD-like NCI-H1299 (TP53

resultsSAHA reprogrammed the transcriptome in both lines (1,098 DEGs in H1299; 1,532 in H1703), enforcing a shared suppression of E2F/G2-M programs but diverging in non-cell-cycle outputs. In LUAD-like H1299, SAHA upregulated morphogenesis/adhesion and KRAS_SIGNALING_DN/EMT-adjacent signatures while dampening interferon/stress pathways, and significantly reduced migration at low dose. In LUSC-like H1703, SAHA triggered a dominant cell-cycle checkpoint shutdown coupled to complement/ECM and inflammatory induction, with stronger apoptosis but only modest short-term migration restraint. Survival-anchored analysis yielded four SAHA feature-sensing modules; the LUAD_RISK module was enriched for cell-cycle/mitotic genes and was attenuated by SAHA, whereas the LUSC_RISK module captured checkpoint, ECM, and stress-response programs preferentially down-regulated in H1703. Both risk modules stratified prognosis and were linked to distinct HDAC-centred neighbourhoods (HDAC7/9-LUAD_RISK and HDAC4/6-LUSC_RISK) in TCGA tumours.

conclusionsSAHA imposes a common anti-proliferative core but engages distinct lineage-conditioned risk modules in LUAD and LUSC-cell-cycle/migration-linked in LUAD and checkpoint/stress-linked in LUSC. These SAHA feature-sensing modules provide a mechanistic and clinically anchored framework for subtype-tailored HDAC-directed combinations and for future development of HDACi-aligned biomarkers in NSCLC.

Indexed as

Adenocarcinoma of LungCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHistone Deacetylase InhibitorsLung NeoplasmsTranscriptomeVorinostatApoptosisCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansHistone Deacetylase InhibitorsVorinostatHDAC inhibitorsNSCLCPersonalized therapySAHATranscriptomic modulation

Identifiers

PMID41593801
PMCPMC12918457

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