The H3K4 methyltransferase SETD1A is required for proliferation of non-small cell lung cancer cells by promoting S-phase progression

Kang, Joo-Young; Park, Jin Woo; Hwang, Yusang; Hahm, Ja Young; Park, Jun-Young; Park, Kwon-Sik; Seo, Sang-Beom

doi:10.1016/j.bbrc.2021.05.026

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…As shown in Figure 1 and Table S1, SETD1A overexpression was correlated with venous invasion and worse prognosis with PDAC. A clinical association between SETD1A overexpression and poor survival has also been reported in cancers, 17,18,20 and higher SETD1A levels are associated with a more advanced clinical stage, vascular invasion, and metastasis in triple‐negative breast cancer 27 . Therefore, SETD1A plays a pivotal role in the malignant progression of diverse cancer types, including PDAC.…”

Section: Discussionmentioning

confidence: 87%

“…SETD1A has also been shown to be essential for maintaining mitosis and cell proliferation 15 . According to previous studies, SETD1A expression is upregulated in various cancers, and its overexpression accelerates cell proliferation, invasiveness, and tumorigenicity 16–18 . Although SETD1A contributes to genome‐wide H3K4me3 deposition and some target genes of SETD1A were recently found in gastric cancer cells, 19 the molecular mechanism underlying SETD1A overexpression as well as the target genes associated with H3K4me3 have not yet been elucidated in PDAC.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer

et al. 2022

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Although histone H3K4 methyltransferase SETD1A is overexpressed in various cancer types, the molecular mechanism underlying its overexpression and its target genes in pancreatic ductal adenocarcinoma (PDAC) remain unclarified. We conducted immunohistochemical staining for SETD1A in 105 human PDAC specimens to assess the relationship between SETD1A overexpression and clinicopathological features. The function and target genes of SETD1A were investigated using human pancreatic cancer cell lines. SETD1A expression was upregulated in 51.4% of patients with PDAC and was an independent prognostic factor associated with shorter disease‐free survival after resection (p < 0.05). Knockdown and overexpression of SETD1A showed that SETD1A plays a crucial role in increasing the proliferation and motility of PDAC cells. SETD1A overexpression increased tumorigenicity. RNA sequencing of SETD1A‐knockdown cells revealed downregulation of RUVBL1, an oncogenic protein ATP‐dependent DNA helicase gene. ChIP analysis revealed that SETD1A binds to the RUVBL1 promoter region, resulting in increased H3K4me3 levels. Knockdown of RUVBL1 showed inhibition of cell proliferation, migration, and invasion of PDAC cells, which are similar biological effects to SETD1A knockdown. High expression of both SETD1A and RUVBL1 was an independent prognostic factor not only for disease‐free survival but also for overall survival (p < 0.05). In conclusion, we identified RUVBL1 as a novel downstream target gene of the SETD1A‐H3K4me3 pathway. Co‐expression of SETD1A and RUVBL1 is an important factor for predicting the prognosis of patients with PDAC.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer

et al. 2022

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“…SETD1A, a lysine-methyltransferase (lysine-methyltransferase), has been shown to be a risk gene for schizophrenia associated with cognitive impairment, and its mutation increases the risk of schizophrenia (Mukai et al 2019 ; Singh et al 2016 ). Enhanced SETD1A is associated with the occurrence and metastasis of a variety of tumors (Kang et al 2021 ; Wu et al 2020 ; Yang et al 2020 ). SETD1A can also prevent aging by regulating mitotic gene expression procedures (Tajima et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Chromatin Regulatory Factors Related to Immunity and Treatment of Alzheimer’s Disease

Xiong

Wang

et al. 2023

J Mol Neurosci

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Alzheimer’s disease is one of the common neurodegenerative diseases in the elderly, which mainly manifests as progressively severe cognitive impairment, which seriously affects the quality of life of patients. Chromatin regulators have been shown to be associated with a variety of biological processes, and we mainly explore the relationship between chromatin regulators and Alzheimer’s disease. Eight hundred seventy chromatin regulators were collected from previous studies, and data related to Alzheimer’s disease patients were downloaded from the GEO database. Finally, we screened chromatin regulators related to Alzheimer's disease immunity, established prediction models, and screened related drugs and miRNAs. We screened 160 differentially expressed CRs, constructed an interaction network, obtained 10 hub genes, successfully constructed a prediction model based on immune-related 5 CRs, and obtained 520 related drugs and 3 related miRNA, which provided an idea for the treatment of Alzheimer's disease. Our study identified 5 chromatin regulators related to Alzheimer’s disease, which are expected to be new targets for Alzheimer’s disease immunotherapy.

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“…In A549 and H1299 cells, SETD1A shows an increased expression trend 9 . In addition, SETD1A is essential for the proliferation of NSCLC cells during the progression to the S phase, thus contributing to NSCLC development 10,11 . Nevertheless, its engagement in NSCLC cell ferroptosis is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

SETD1A‐mediated H3K4me3 methylation upregulates lncRNA HOXC‐AS3 and the binding of HOXC‐AS3 to EP300 and increases EP300 stability to suppress the ferroptosis of NSCLC cells

Shi,

Zhang,

Shen

et al. 2023

Thoracic Cancer

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BackgroundHistone methyltransferases are crucial regulators in non‐small cell lung cancer (NSCLC) development. This study explored the mechanism of histone methyltransferase SET domain containing 1A (SETD1A)‐mediated H3K4me2 methylation in NSCLC cell ferroptosis and provides novel targets for NSCLC treatment.MethodsUpon downregulation of SETD1A in NSCLC cell lines, cell proliferation potential, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities, iron content, and SETD1A, long noncoding RNA HOXC cluster antisense RNA 3 (lncRNA HOXC‐AS3), E1A binding protein p300 (EP300), glutathione peroxidase 4 (GPX4) expressions were determined via cell counting kit‐8, ELISA, iron assay kits, RT‐qPCR, and western blot. Enrichment levels of SETD1A and H3K4me3 in the HOXC‐AS3 promotor were measured via chromatin immunoprecipitation, and the binding of HOXC‐AS3 and EP300 was analyzed via RNA immunoprecipitation. Rescue experiments were performed to confirm their roles in NSCLC cell ferroptosis. Xenograft tumor models were established to validate the role of SETD1A in vivo.ResultsSETD1A, H3K4me3, HOXC‐AS3, and EP300 were highly‐expressed in NSCLC cells. Silencing SETD1A inhibited NSCLC cell proliferation, increased MDA and iron levels, and decreased SOD, GSH, and GPX4 levels. SETD1A downregulation reduced H3K4me3 level, HOXC‐AS3 expression, the binding of HOXC‐AS3 to EP300, and EP300 stability. Overexpression of HOXC‐AS3 or EP300 reversed the promotion of silencing SETD1A on NSCLC cell ferroptosis. Silencing SETD1A reduced tumor volume and weight and positive rate of ki67 and increased ferroptosis through the HOXC‐AS3/EP300 axis.ConclusionSETD1A‐mediated H3K4me2 methylation promoted HOXC‐AS3 expression, binding of HOXC‐AS3 to EP300, and EP300 stability, thereby suppressing NSCLC cell ferroptosis.

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The H3K4 methyltransferase SETD1A is required for proliferation of non-small cell lung cancer cells by promoting S-phase progression

Cited by 8 publications

References 26 publications

Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer

Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer

Identification of Chromatin Regulatory Factors Related to Immunity and Treatment of Alzheimer’s Disease

SETD1A‐mediated H3K4me3 methylation upregulates lncRNA HOXC‐AS3 and the binding of HOXC‐AS3 to EP300 and increases EP300 stability to suppress the ferroptosis of NSCLC cells

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