Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression in Cancer

Tran, Trac D.; Lowman, Xazmin H.; Kong, Mei

doi:10.1158/1078-0432.ccr-16-2506

Cited by 70 publications

(44 citation statements)

References 72 publications

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“…Epigenetic alterations such as DNA methylation, histone modification and chromatin remodeling have been implicated in the initiation and progression of cancers including SCCHN 4 , 5 . Histone methylation, as one kind of histone modification, affects gene expression by directly altering chromatin structure and/or by promoting the recruitment of effector proteins 6 . Trimethylated lysine 4 on histone H3 (H3K4me3), an epigenetic marker, shows abnormal expression and function in diverse solid tumors 7 .…”

Section: Introductionmentioning

confidence: 99%

KDM5B overexpression predicts a poor prognosis in patients with squamous cell carcinoma of the head and neck

Huang

Qiu

et al. 2018

J. Cancer

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Purpose: Lysine demethylase (KDM) 5B, as a member of the histone lysine demethylase family, is overexpressed and functions abnormally in various human cancers. However, its expression in the squamous cell carcinoma of the head and neck (SCCHN) remains unclear.Methods: KDM5B expression was analyzed by immunohistochemistry and correlated with clinicopathological parameters in 103 archival SCCHN tissue samples and 24 adjacent noncancerous epithelial tissues.Results: We found that KDM5B expression was higher in SCCHN than that in adjacent noncancerous tissues. This was closely associated with lymph node metastasis and tumor recurrence. In addition, Kaplan-Meier analysis revealed that patients with high KDM5B expression had shorter disease-free and overall survival times than those with low KDM5B expression. Importantly, both univariate and multivariate analysis demonstrated that KDM5B level was an independent prognostic factor in SCCHN patients.Conclusions: These results indicate that KDM5B is a valuable biomarker that can be used to predict SCCHN patient outcome.

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Section: Introductionmentioning

confidence: 99%

KDM5B overexpression predicts a poor prognosis in patients with squamous cell carcinoma of the head and neck

Huang

Qiu

et al. 2018

J. Cancer

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“…Metabolism‐driven epigenetic changes can influence cancer risk. [ 16 ] In mammalian cells, the set of genes activated by the c‐Myc oncoprotein [ 17 ] through metabolic rewiring and chromatin remodeling [ 18 ] resembles the set of growth genes that are acetylated during acetyl‐CoA peak abundance in the yeast cell cycle. [ 2,7,8 ] Metabolic gene mutations in diverse cancers cause an accumulation of succinate, fumarate, and R‐2‐hydroxyglutarate.…”

Section: Metabolism–histone Interactions Regulate Normal and Disease mentioning

confidence: 99%

Nutrient Sensing by Histone Marks: Reading the Metabolic Histone Code Using Tracing, Omics, and Modeling

Campit

Meliki²,

Youngson

et al. 2020

BioEssays

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Several metabolites serve as substrates for histone modifications and communicate changes in the metabolic environment to the epigenome. Technologies such as metabolomics and proteomics have allowed us to reconstruct the interactions between metabolic pathways and histones. These technologies have shed light on how nutrient availability can have a dramatic effect on various histone modifications. This metabolism–epigenome cross talk plays a fundamental role in development, immune function, and diseases like cancer. Yet, major challenges remain in understanding the interactions between cellular metabolism and the epigenome. How the levels and fluxes of various metabolites impact epigenetic marks is still unclear. Discussed herein are recent applications and the potential of systems biology methods such as flux tracing and metabolic modeling to address these challenges and to uncover new metabolic–epigenetic interactions. These systems approaches can ultimately help elucidate how nutrients shape the epigenome of microbes and mammalian cells.

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“…Traditionally, epigenetic regulation refers to diverse and reversible chemical modi cations on DNA or histones. Among these diverse modi cations, histone methylation at different sites lead to increased or inhibited gene expression, which regulate gene expression in a way independent to genome changes [4,5].…”

Section: Introductionmentioning

confidence: 99%

Histone Methyltransferase WHSC1 Inhibits Colorectal Cancer Cell Apoptosis via Targeting Anti-apoptotic BCL2

Wang

Tang

Guo

et al. 2020

Preprint

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Background: WHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. Colorectal cancer (CRC) is the 4th deadliest and 3rd most frequent cancer globally. However, the role of WHSC1 in CRC progression remains unknown. Methods: qRT-PCR, immunoblotting assays (WB), and immunohistochemistry (IHC) staining was performed to investigate WHSC1 expression levels in CRC tissues and normal tissues. CCK-8 assays, colony formation assays, and flow cytometry were also used to assess the effect of WHSC1 depletion in CRC cell proliferation, apoptosis and oxaliplatin sensitivity in vitro. A cell line-derived xenograft model in nude mice was performed to determine the role of WHSC1 in CRC cell apoptosis in vivo. Results: WHSC1 as well as H3K36me2 were highly expressed in clinical CRC tissues compared with in normal counterparts. High WHSC1 expression was correlated with poorer prognosis in CRC patients. Knockdown of WHSC1 significantly promoted CRC cell apoptosis and inhibited tumour growth in vivo. Further mechanistic investigation revealed that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level, so BCL2 expression is markedly decreased after WHSC1 depletion. Conclusions: Our findings demonstrated that knockdown of WHSC1 promoted colon cancer cell apoptosis and suppressed CRC tumorigenesis through targeting BCL2 transcription, suggesting WHSC1 activity may be a potential therapeutic target for the treatment of CRC.

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Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression in Cancer

Cited by 70 publications

References 72 publications

KDM5B overexpression predicts a poor prognosis in patients with squamous cell carcinoma of the head and neck

KDM5B overexpression predicts a poor prognosis in patients with squamous cell carcinoma of the head and neck

Nutrient Sensing by Histone Marks: Reading the Metabolic Histone Code Using Tracing, Omics, and Modeling

Histone Methyltransferase WHSC1 Inhibits Colorectal Cancer Cell Apoptosis via Targeting Anti-apoptotic BCL2

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