Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

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RNA modifications in cancer

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

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HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Cancer Science, Journal Year: 2023, Volume and Issue: 114(5), P. 1830 - 1845

Published: Jan. 31, 2023

Immune microenvironment could affect the biological progress in prostate cancer (PCa) through N6 methyl adenosine (m6A) methylation. The purpose of this study was to investigate crosstalk between m6A methylation and immune explore potential biomarkers improve immunotherapeutic response. Firstly, according 11 differentially expressed genes normal tumor samples, PCa patients were divided into subtype 1 (IMS1) IMS2 based on gene profiles extracted from Cancer Genome Atlas (TCGA) database. showed an "cold" phenotype with worse prognoses, HNRNPC identified as biomarker by protein-protein interaction network. Furthermore, bioinformatics analyses vitro experiments, we found that HNRNPC-high a suppressive immune-infiltrating higher infiltration regulatory T (Treg) cells. Finally, cocultured transfected cells peripheral blood mononuclear (PBMC) verified inhibits immunity elevating activation Treg suppression effector CD8 cell. In conclusion, PCa, regulating Activation targeting may be therapeutic option for advanced PCa.

Language: Английский

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N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 3, 2023

Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC).Totals of 371 HCC 50 normal were included this study. GSE121248 GSE40367 datasets used validate expression HNRNPC. The R package "ConsensusClusterPlus" was performed screen consensus clustering types based on HCC. "pheatmap", "immunedeconv", "survival", "survminer" "RMS" applied investigate expression, immunity, overall survival, clinical application different clusters groups. Comprehensive analysis HNRNPC pan-cancer conducted by TIMER2 database. Besides, mRNA protein verified qRT-PCR immunohistochemistry analysis.Most over-expressed excerpt ZC3H13 Three independent screened cluster 2 had favorable prognosis Then, positively macrophage, hematopoietic stem cell, endothelial stroma score, while negatively T cell CD4+ memory mast cell. We identified an prognostic factor HCC, nomogram superior value decision making. Moreover, PD-L1 significantly up-regulated tissues, 1, 3, we found correlated Patients high-expression groups associated tumor-promoting cells. prognosis, TMB, checkpoints cancers. Particularly, experiments confirmed that cells tissues.The play irreplaceable roles infiltration relationship possesses promising direction targets immunotherapy response. Exploration pattern could be build stratification individual move toward personalized treatment.

Language: Английский

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Targeting the prostate tumor microenvironment by plant-derived natural products

Cellular Signalling, Journal Year: 2023, Volume and Issue: 115, P. 111011 - 111011

Published: Dec. 15, 2023

Language: Английский

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RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1303 - 1303

Published: March 27, 2024

N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays crucial role in regulating mRNA expression, stability, and translation mammals. M6A regulators have gained attention for their potential implications tumorigenesis clinical applications, such as cancer diagnosis therapeutics. The existing literature predominantly addresses m6A the context of primary prostate (PCa). However, notable gap knowledge emerges regarding dynamic expression patterns these PCa progresses towards castration-resistant stage (CRPC). Employing sequential window acquisition all theoretical mass spectra (SWATH-MS) RNAseq analysis, we comprehensively profiled 27 hormone/androgen-dependent -independent cell lines, revealing distinct clustering between tumor adjacent normal tissues. High-grade tumors demonstrated upregulation METTL3, RBM15B, HNRNAPA2B1 downregulation ZC3H13, NUDT21, FTO. Notably, identified six associated with survival. Additionally, association analysis PCa-associated risk loci genome atlas program (TCGA) data unveiled genetic variations near WTAP, HNRNPA2B1, FTO genes significant quantitative trait loci. In summary, our study unraveled abnormalities regulator progression, elucidating Considering heterogeneity within phenotypes treatment responses, findings suggest that prognostic stratification based on could enhance prognosis.

Language: Английский

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Heterogeneous nuclear ribonucleoprotein C promotes non-small cell lung cancer progression by enhancing XB130 mRNA stability and translation

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 13, 2025

XB130, a classical adaptor protein, exerts critical role in diverse cellular processes. Aberrant expression of XB130 is closely associated with tumorigenesis and aggressiveness. However, the mechanisms governing its regulation remain poorly understood. Heterogeneous nuclear ribonucleoprotein C (hnRNPC), as an RNA-binding known to modulate multiple aspects RNA metabolism has been implicated pathogenesis various cancers. We have previously discovered that hnRNPC one candidate proteins interact 3' untranslated region (3'UTR) non-small cell lung cancer (NSCLC). Therefore, this study aims comprehensively elucidate how regulates NSCLC. evaluated assessed correlation between prognosis patients using public databases. Subsequently, several stable lines were constructed. The proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) these cells detected through Real-time analysis, adherent colony formation, wound healing assay, invasion Western blotting. specific regulatory manner was investigated by quantitative PCR, blotting, pull‑down dual‑luciferase reporter immunoprecipitation, Co-Immunoprecipitation. identified significantly elevated NSCLC correlates poor adenocarcinoma. HnRNPC overexpression increased subsequently activating PI3K/Akt signaling pathway ultimately promoting proliferation EMT. Additionally, overexpressing hnRNPC-silenced partially restored Mechanistically, specifically bound 3'UTR segments mRNA, enhancing mRNA stability inhibiting recruitment nucleases 5'-3' exoribonuclease 1 (XRN1) DIS3-like 3'-5' 2 (DIS3L2). Furthermore, simultaneously interacted eukaryotic initiation factor 4E (eIF4E), component eIF4F complex, facilitating circularization thereby increasing translation efficiency. promotes progression translation, suggesting might be potential therapeutic prognostic target for

Language: Английский

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Abnormal changes in metabolites caused by m6A methylation modification: The leading factors that induce the formation of immunosuppressive tumor microenvironment and their promising potential for clinical application

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 1, 2024

N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within tumor microenvironment (TME) and are essential for meeting demands cellular growth maintaining tissue homeostasis, enabling cells to adapt specific conditions TME. An increasing number research studies focused on role m6A glucose, amino acid lipid metabolism, revealing their capacity induce aberrant changes metabolite levels. These may turn trigger oncogenic signaling pathways, leading substantial alterations Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids cholesterol, exhibit pronounced deviations from normal not only foster tumorigenesis, proliferation angiogenesis but also give rise an immunosuppressive TME, thereby facilitating immune evasion by tumor. The primary objective this review is comprehensively discuss regulatory aforementioned metabolites potential impact development TME through alterations. This aims elaborate intricate networks governed m6A-metabolite-TME axis underscores its pivotal progression. Furthermore, we delve into implications novel targeted therapeutic strategies cancer research.

Language: Английский

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Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 219 - 237

Published: Feb. 1, 2025

Abstract: Prostate cancer is prevalent among men aged 65 and older. Bone metastasis occurs in up to 90% of advanced prostate patients, metastatic generally considered a non-curative condition which can impact quality life. The tumor microenvironment, comprising diverse cellular non-cellular elements, interacts with cells affect growth bone metastasis. Within the different cell types, including osteoblasts, osteoclasts, adipocytes, endothelial cells, hematopoietic stem immune engage cells. Some alter behavior, while others are impacted or overpowered by leading phases movement, dormancy, latency, resistance treatment, advancement visible This review summarizes recent research on microenvironment metastasis, exploring underlying mechanisms potential value targeting these environments for treatment. Keywords: cancer, epithelial-mesenchymal transition, dormancy

Language: Английский

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RNA modifications in the tumor microenvironment: insights into the cancer-immunity cycle and beyond

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 2, 2025

Language: Английский

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