Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Abstract Acquired resistance remains a bottleneck for molecular‐targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib‐resistant models, increased glycolysis leads lactate accumulation lysine lactylation IGF2BP3. This is crucial capturing PCK2 NRF2 mRNAs, thereby enhancing their expression. process reprograms serine metabolism strengthens the antioxidant defense system. Additionally, altered increases availability methylated substrates, such S‐adenosylmethionine (SAM), N6‐methyladenosine (m6A) methylation mRNAs. The lactylated IGF2BP3‐PCK2‐SAM‐m6A loop maintains elevated levels, system promoting lenvatinib HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or inhibitor 2‐DG restored sensitivity vivo. These findings highlight connection between metabolic reprogramming regulation suggest pathways offer new strategies overcome

Язык: Английский

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Small-molecule-based targeted therapy in liver cancer

Molecular Therapy, Год журнала: 2024, Номер 32(10), С. 3260 - 3287

Опубликована: Авг. 8, 2024

Язык: Английский

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Methylomics and cancer: the current state of methylation profiling and marker development for clinical care

Cancer Cell International, Год журнала: 2023, Номер 23(1)

Опубликована: Окт. 16, 2023

Abstract Epigenetic modifications have long been recognized as an essential level in transcriptional regulation linking behavior and environmental conditions or stimuli with biological processes disease development. Among them, methylation is the most abundant of these reversible epigenetic marks, predominantly occurring on DNA, RNA, histones. Methylation modification intimately involved regulating gene transcription cell differentiation, while aberrant status has linked cancer development several malignancies. Early detection precise restoration dysregulated form basis for epigenetics-based therapeutic strategies. In this review, we summarize current basic understanding mechanisms responsible cover cutting-edge research techniques detecting across genome transcriptome. We then explore recent advances clinical diagnostic applications markers various cancers address state future prospects therapies different diseases, especially comparing pharmacological methylase/demethylase inhibitors CRISPRoff/on editing systems. This review thus provides a resource emerging role cancer, use methylation-based biomarkers detection, novel methylation-targeted drugs.

Язык: Английский

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Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(3)

Опубликована: Март 1, 2024

Abstract As single‐cell RNA sequencing enables the detailed clustering of T‐cell subpopulations and facilitates analysis metabolic states metabolite dynamics, it has gained prominence as preferred tool for understanding heterogeneous cellular metabolism. Furthermore, synergistic or inhibitory effects various pathways within T cells in tumour microenvironment are coordinated, increased activity specific generally corresponds to functional activity, leading diverse behaviours related immune cells, which shows potential tumour‐specific induce persistent responses. A holistic how heterogeneity governs function subsets is key obtaining field‐level insights into immunometabolism. Therefore, exploring mechanisms underlying interplay between metabolism functions will pave way precise immunotherapy approaches future, empower us explore new methods combating tumours with enhanced efficacy.

Язык: Английский

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Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11544 - 11544

Опубликована: Июль 17, 2023

MicroRNAs are small, noncoding molecules of about twenty-two nucleotides with crucial roles in both healthy and pathological cells. Their expression depends not only on genetic factors, but also epigenetic mechanisms like genomic imprinting inactivation X chromosome females that influence a sex-dependent manner onset, progression, response to therapy different diseases cancer. There is evidence correlation between miRNAs, sex, cancer solid tumors hematological malignancies; as an example, lymphomas, prevalence rate higher men than women, miR-142 “silenced” because its hypermethylation by DNA methyltransferase-1 it blocked normal activity regulating the migration cell. This condition corresponds clinical practice more aggressive tumor. In addition, treatment can have advantages from evaluation miRNAs expression; fact, estrogens hepatocellular carcinoma determines upregulation oncosuppressors miR-26a, miR-92, miR-122 and, consequently, apoptosis. The aim this review present exhaustive collection scientific data possible role sex differences through which cancerogenesis, autophagy, apoptosis cells diverse types tumors.

Язык: Английский

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SETDB1: Progress and prospects in cancer treatment potential and inhibitor research

Bioorganic Chemistry, Год журнала: 2024, Номер 145, С. 107219 - 107219

Опубликована: Фев. 17, 2024

Язык: Английский

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Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis

APOPTOSIS, Год журнала: 2024, Номер 29(9-10), С. 1632 - 1647

Опубликована: Май 17, 2024

Язык: Английский

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Suv39h1 contributes to activation of hepatic stellate cells in non-alcoholic fatty liver disease by enabling anaerobic glycolysis

Life Sciences, Год журнала: 2024, Номер 341, С. 122498 - 122498

Опубликована: Фев. 8, 2024

Язык: Английский

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Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

Genes & Diseases, Год журнала: 2024, Номер 11(5), С. 101285 - 101285

Опубликована: Апрель 4, 2024

Cancer stem cells (CSCs) play a crucial role in tumor initiation, recurrence, metastasis, and drug resistance. However, the current understanding of CSCs hepatocellular carcinoma (HCC) remains incomplete. Through comprehensive analysis database, it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), critical enzyme involved cholesterol metabolism, is up-regulated HCC tissues liver CSCs. Moreover, high expression HMGCR associated with poor prognosis patients HCC. Functionally, promotes stemness metastasis both vitro vivo. By screening various signaling pathway inhibitors, we have determined regulates by activating Hedgehog Mechanistically, positively correlates Smoothened receptor facilitates nuclear translocation transcriptional activator GLI family zinc finger 1. Inhibition can reverse stimulatory effects on Notably, simvastatin, an FDA-approved cholesterol-lowering drug, shown to inhibit targeting HMGCR. Taken together, our findings suggest regeneration through activation signaling, simvastatin holds potential for clinical suppression metastasis.

Язык: Английский

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Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Metabolites, Год журнала: 2024, Номер 14(6), С. 325 - 325

Опубликована: Июнь 8, 2024

Epigenetic and metabolic reprogramming alterations are two important features of tumors, their reversible, spatial, temporal regulation is a distinctive hallmark carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, new entry point for tumor therapy. Moreover, drives hepatocellular carcinoma (HCC) initiation progression, highlighting significance metabolism in this disease. Exploring inter-regulatory relationship between epigenetic modification has become one hot directions current research. As viral etiologies have given way to dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it urgent that complex molecular pathways linking them hepatocarcinogenesis be explored. However, how aberrant crosstalk modifications affects MASLD-induced HCC lacks comprehensive understanding. A better understanding linkages necessary improve treatment strategies. For reason, review examines interwoven landscape carcinogenesis context focusing regulating development interactions while also updating advances modification-based therapeutic drugs HCC.

Язык: Английский

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