<i>F. nucleatum</i> targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer

Hong, Jie; Guo, Fangfang; Lu, Su; Shen, Chaoqin; Ma, Dan; Zhang, Xinyu; Xie, Yile; Yan, Tingting; Yu, TaChung; Sun, Tiantian; Qian, Yun; Zhong, Ming; Chen, Jinxian; Peng, Yanshen; Wang, Cheng; Zhou, Xiang; Li, Jianjun; Liu, Qiang; Ma, Xiong; Chen, Yingxuan; Chen, Haoyan; Fang, Jing‐Yuan

doi:10.1136/gutjnl-2020-322780

Cited by 158 publications

(148 citation statements)

References 49 publications

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“…Previously, Hong et al (2020) reported histone acetylation of specific genes following Fn-induced lncRNA ENO1-IT upregulation. To our knowledge, our present study is the first to explore epigenome-wide changes in host chromatin in response to Fn exposure.…”

Section: Discussionmentioning

confidence: 98%

Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum

Despins¹,

Brown

Robinson

et al. 2021

Preprint

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Fusobacterium nucleatum (Fn) is a ubiquitous opportunistic pathogen with an emerging role as an oncomicrobe in colorectal and other cancer types. Fn can adhere to and invade host cells in a manner that varies across Fn strains and host cell phenotypes. Here we performed pairwise co-cultures between three Fn strains and two immortalized primary host cell types (colonic epithelial cells and vascular endothelial cells) followed by RNA-seq and ChIP-seq to investigate transcriptional and epigenetic host cell responses. We observed that Fn-induced host cell transcriptional modulation involves strong upregulation of genes related to immune migration and inflammatory processes, such as TNF, CXCL8, CXCL1, and CCL20. Further, we identified genes strongly upregulated specifically in conditions of host cell invasion, including overexpression of both EFNA1 and LIF, two genes commonly upregulated in colorectal cancer and associated with poor patient outcomes, and PTGS2 (COX2), a gene associated with the protective effect of aspirin in the colorectal cancer setting. Interestingly, we also observed downregulation of numerous histone modification genes upon Fn exposure. To further explore this relationship, we used the ChIP-seq data to annotate chromatin states genome-wide. We found significant chromatin remodeling following Fn exposure in conditions of host cell invasion, with substantial increases in the frequency of states corresponding to active enhancers as well as low signal or quiescent states. Thus, our results highlight increased inflammation and chemokine gene expression as conserved host cell responses to Fn exposure, and extensive host cell epigenomic changes associated with Fn host cell invasion. These results extend our understanding of Fn as an emerging pathogen and highlight the importance of considering strain heterogeneity and host cell phenotypic variation when exploring pathogenic mechanisms of Fn.

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Section: Discussionmentioning

confidence: 98%

Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum

Despins¹,

Brown

Robinson

et al. 2021

Preprint

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“…Upregulated ENO1-IT activates the target genes including ENO1, resulting in elevated glycolysis and enhanced tumor growth. 147 HIF-1α induces upregulation of lncRNA AC020978 in NSCLC. Elevated AC020978 stabilizes PKM2 by protecting it from degradation.…”

Section: Transcriptional Regulationmentioning

confidence: 99%

“…Upregulated ENO1-IT activates the target genes including ENO1, resulting in elevated glycolysis and enhanced tumor growth. 147 …”

Section: Deregulated Mechanisms Of Lncrnas In Cancer Glycolysismentioning

confidence: 99%

Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives

Huang¹,

Zhu²,

Liang³

et al. 2021

CMAR

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Cancer cells exhibit distinct metabolic characteristics that employ glycolysis to provide energy and intermediary metabolites. This aberrant metabolic phenotype favors cancer progression. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. LncRNAs contribute to cancer progression and therapeutic resistance and affect aerobic glycolysis via multiple mechanisms, including modulating glycolytic transporters and enzymes. Further, dysregulated signaling pathways are vital for glycolysis. In this review, we highlight regulatory mechanisms for lncRNAs in aerobic glycolysis that provide novel insights into cancer development. Moreover, a comprehensive understanding of the regulatory mechanisms of lncRNAs in aerobic glycolysis can provide new strategies for clinical cancer management.

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“…Interestingly, even microorganisms may modify glucose metabolism in cancer via lncRNAs. Fusobacterium nucleatum, a member of the normal flora in the oral cavity, activates lncRNA ENO1-IT1 transcription that eventually induces glucose metabolism in colorectal cancer (CRC) [30].…”

Section: Lncrnas Regulates Pathophysiological Processes In Cancer Via the Influence Of Glucose Metabolismmentioning

confidence: 99%

Involvement of Long Non-Coding RNAs in Glucose Metabolism in Cancer

Balihodzic

Barth

Prinz

et al. 2021

Cancers

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The rapid and uncontrolled proliferation of cancer cells is supported by metabolic reprogramming. Altered glucose metabolism supports cancer growth and progression. Compared with normal cells, cancer cells show increased glucose uptake, aerobic glycolysis and lactate production. Byproducts of adjusted glucose metabolism provide additional benefits supporting hallmark capabilities of cancer cells. Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts of more than 200 nucleotides in length. They regulate numerous cellular processes, primarily through physical interaction with other molecules. Dysregulated lncRNAs are involved in all hallmarks of cancer including metabolic alterations. They may upregulate metabolic enzymes, modulate the expression of oncogenic or tumor-suppressive genes and disturb metabolic signaling pathways favoring cancer progression. Thus, lncRNAs are not only potential clinical biomarkers for cancer diagnostics and prediction but also possible therapeutic targets. This review summarizes the lncRNAs involved in cancer glucose metabolism and highlights their underlying molecular mechanisms.

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F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer

Cited by 158 publications

References 49 publications

Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum

Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum

Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives

Involvement of Long Non-Coding RNAs in Glucose Metabolism in Cancer

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