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SAS shKDM4C cell line RNA sequencing

ABSTRACT: This study uses RNA-seq analysis to explore the impact of KDM4C, a histone lysine demethylase, on head and neck squamous cell carcinoma (HNSCC). KDM4C modifies histone proteins by removing methyl groups from H3K9me3/2, which affects gene expression. The study focuses on the role of KDM4C in SAS cells, a type of HNSCC cell line, specifically concerning metastasis. Gene Set Enrichment Analysis analyzed RNA-seq data comparing SAS cells with and without KDM4C depletion (sh4C#1 vs. LKO). The result showed that KDM4C significantly influences various metabolic processes, including heme metabolism, peroxisome function, and bile acid metabolism in SAS cells. Additionally, the study performed a KDM4C-ChIP seq analysis on SAS cells to gain further insight into its role. According to Enrichr analysis, GATA1 was the top-ranking transcription factor in these pathways, suggesting its potential interaction with KDM4C in HNSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252493 | GEO | 2025/04/30

REPOSITORIES: GEO

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Project description:Background: The sensitivity of head and neck squamous cell carcinoma (HNSCC) to ionizing radiation, among others, is determined by the number of cells with high clonogenic potential and stem-like features. These cellular characteristics are dynamically regulated in response to treat-ment and may lead to an enrichment of radioresistant cells with a cancer stem cell (CSC) pheno-type. Epigenetic mechanisms, particularly DNA and histone methylation, are key regulators of gene-specific transcription and cellular plasticity. Therefore, we hypothesized that specific epi-genetic targeting may prevent irradiation-induced plasticity and may sensitize HNSCC cells to radiotherapy. Methods: We compared the DNA methylome and intracellular concentrations of tricarboxylic acid cycle metabolites in radioresistant FaDu and Cal33 cell lines with their parental controls, as well as aldehyde dehydrogenase (ALDH)-positive CSCs with negative controls. Moreover, we conducted a screen of a chemical library targeting enzymes in-volved in epigenetic regulation in combination with irradiation and analyzed the clonogenic potential, sphere formation, and DNA repair capacity to identify compounds with both radiosensi-tizing and CSC-targeting potential. Results: We identified the histone demethylase inhibitor GSK-J1, which targets UTX (KDM6A) and JMJD3 (KDM6B), leading to increased H3K27 tri-methylation, heterochromatin formation, and gene silencing. The clonogenic survival assay after siRNA-mediated knock-down of both genes radiosensitized Cal33 and SAS cell lines. Moreover, high KDM6A expression in tissue sections of patients with HNSCC was associated with improved locoregional control after primary (n = 137) and post-operative (n = 187) radio/chemotherapy. Conversely, high KDM6B expression was a prognostic factor for reduced overall survival. Conclusions: Within this study, we investigated cellular and molecular mechanisms underlying irradiation-induced cellular plasticity, a key inducer of radioresistance, with a focus on epigenetic alterations. We identified UTX (KDM6A) as a putative prognostic and therapeutic target for HNSCC patients treated with radiotherapy.

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SAS shKDM4C cell line RNA sequencing

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