Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

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Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1049 - 1082

Published: Oct. 20, 2022

Reversible, spatial, and temporal regulation of metabolic reprogramming epigenetic homeostasis are prominent hallmarks carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature human cancers, which contributes tumorigenesis maintenance malignant phenotypes by regulating gene expression. The epigenome sensitive changes. Metabolism produces various metabolites that substrates, cofactors, or inhibitors enzymes. Alterations in pathways fluctuations intermediate convey information regarding intracellular status into nucleus modulating activity enzymes thus remodeling landscape, inducing transcriptional responses heterogeneous requirements. regulated machinery at both post-transcriptional levels. modifiers, chromatin remodelers non-coding RNAs integral contributors regulatory networks involved cancer metabolism, facilitating transformation. However, significance close connection between epigenetics context has not been fully deciphered. Thus, it will be constructive summarize update emerging new evidence supporting this bidirectional crosstalk deeply assess how abnormalities could exploited optimize treatment paradigms establish therapeutic options. In review, we central mechanisms reciprocally modulate each other elaborate upon major contributions interplays aberrations rewiring initiation development. Finally, highlight potential opportunities hematological malignancies solid tumors targeting epigenetic-metabolic circuit. summary, endeavored depict current understanding coordination these fundamental more comprehensively provide perspectives utilizing targets treatment.

Language: Английский

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circVAMP3 Drives CAPRIN1 Phase Separation and Inhibits Hepatocellular Carcinoma by Suppressing c‐Myc Translation

Advanced Science, Journal Year: 2022, Volume and Issue: 9(8)

Published: Jan. 24, 2022

Previous studies have identified the regulatory roles of circular RNAs (circRNAs) in human cancers. However, molecular mechanisms circRNAs hepatocellular carcinoma (HCC) remain largely unknown. This study screens expression profile HCC and identifies circVAMP3 as a significantly downregulated circRNA tissues. patients with low present poor prognosis. negatively regulates proliferation metastasis cells vitro vivo by driving phase separation CAPRIN1 promoting stress granule formation cells, which can downregulate protein level Myc proto-oncogene inhibiting c-Myc translation. Furthermore, is widely expressed many tissues related Therefore, potential prognostic indicator for may serve therapeutic target treatment.

Language: Английский

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Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: March 29, 2022

Abstract Background Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have identified critical modulator in various cancers. However, the connections between hypoxia circRNAs are largely unknown. Methods Here, we investigated expression profile breast cancer (BC) MCF-7 cells under normoxia using microarray. We novel hypoxia-responsive circRNA named circWSB1, whose pattern, potential diagnostic value prognostic significance were assessed by qRT-PCR situ hybridization. Loss- gain-of-function investigations vivo vitro performed to determine biological functions circWSB1. Mechanistically, chromatin immunoprecipitation dual luciferase reporter assays carried out analyze biogenesis Furthermore, biotin-labeled RNA pull-down, mass spectrometry, immunoprecipitation, fluorescent hybridization, electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation rescue experiments applied investigate interaction circWSB1 Ubiquitin-specific peptidase 10 (USP10) well relationship USP10 p53. Results found that was significantly upregulated BC tissues correlated poor clinical outcomes, which might serve an independent factor for patients. Ectopic promoted proliferation cell vivo. transcriptionally HIF1α response could competitively bind deubiquitinase prevent access p53 cells, leading degradation progression BC. Conclusions Taken together, our findings disclose mechanism hypoxia-inducible interact attenuate mediated stabilization promote BC, providing alternative biomarker therapeutic target

Language: Английский

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circPTEN1, a circular RNA generated from PTEN, suppresses cancer progression through inhibition of TGF-β/Smad signaling

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 8, 2022

Abstract Background PTEN is one of the most frequently mutated genes in human cancer. Although roles canonical protein and isoforms have been extensively explored, current understanding family members cannot fully illustrate diversity their biological processes tumor development. Notably, function noncoding RNAs arising from has less elucidated. Methods We searched circBase circInteractome to analyze potential for generating circRNAs. Then, Sanger sequencing, RNase R Actinomycin D assays were used verify ring structure circPTEN1. In situ hybridization qRT-PCR determine level circPTEN1 peritumor tissues colorectal cancer (CRC). Furthermore, functional experiments, including Transwell assay, 3D multicellular spheroid invasion assay metastasis models, performed using knockdown overexpression cell lines vitro vivo investigate effects on CRC. Mechanistically, luciferase reporter fluorescence hybridization, electrophoretic mobility shift RNA immunoprecipitation, pull-down mass spectrometry executed. Results identified a circular generated gene, designated circPTEN1, that downregulated cancer, decreased expression predicts poor survival. Low promotes PDX models accelerates vitro, whereas reveals opposite roles. Mechanically, we found capable binding MH2 domain Smad4 disrupt its physical interaction with Smad2/3, which reduces formation subsequent nucleus translocation Smad complexes consequently suppresses downstream associated epithelial-mesenchymal transition upon TGF-β stimulation. eIF4A3 cyclization by directly flanking region. Conclusions Our study uncovered novel gene-generated circRNA suppression function, further revealed mechanism CRC mediated TGF-β. The identification provides new direction investigation, elucidation circPTEN1/TGF-β/Smad signaling may pave way development therapeutic strategy progression.

Language: Английский

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