Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101059 - 101059

Опубликована: Янв. 19, 2024

Язык: Английский

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Exosomal circRNAs: Novel biomarkers and therapeutic targets for urinary tumors

Cancer Letters, Год журнала: 2024, Номер 588, С. 216759 - 216759

Опубликована: Фев. 28, 2024

Язык: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Язык: Английский

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Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 8, 2024

Abstract The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study not yet undertaken examining the immunological predictive effects of TUBA1B in pan-carcinoma context. Using data from TCGA, GEO, other databases, we analyzed expression carcinoma types using transcriptional profiling, prognostic implications, genetic epigenetic alterations, methylation patterns, significance. To validate our findings, conducted Western blot analysis assess protein levels matched breast tissue samples performed CCK-8 proliferation assay, flow cytometry, transwell invasion, migration assays comprehensively examine functional impact on cells. Our pan-cancer found upregulation most tumor types, with varying patterns distinct molecular subtypes. High was an independent risk factor associated poor prognoses several cancers, including BRCA, KICH, LGG, LUAD, MESO. also demonstrates moderate high diagnostic accuracy types. Increased m6A were observed gene, while its promoter region displayed low levels. TUBA1B's impacted some cancers by elevating mutation burden, microsatellite instability, neoantigen formation, modulation checkpoints. Functional enrichment highlights TUBA1B’s involvement important cellular processes such as cycle, p53 signaling, senescence, programmed death, regulation immune-related pathways. Moreover, reveals higher tissues compared adjacent tissues. In vitro experiments confirm that deletion reduces proliferation, increasing apoptosis. conclusion, suggests could potentially serve marker for predicting profiles outcomes shed light role cancer, providing solid foundation considering it promising therapeutic target patient treatment.

Язык: Английский

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Combating cisplatin-resistant lung cancer using a coiled-coil lipopeptides modified membrane fused drug delivery system

Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 45 - 58

Опубликована: Янв. 8, 2025

Язык: Английский

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Histone lactylation regulates PRKN-Mediated mitophagy to promote M2 Macrophage polarization in bladder cancer

International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114119 - 114119

Опубликована: Янв. 23, 2025

Язык: Английский

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Glucose homeostasis controls N-acetyltransferase 10-mediated ac4C modification of HK2 to drive gastric tumorigenesis

Theranostics, Год журнала: 2025, Номер 15(6), С. 2428 - 2450

Опубликована: Янв. 20, 2025

Rationale: Abnormal metabolic states contribute to a variety of diseases, including cancer. RNA modifications have diverse biological functions and are implicated in cancer development, gastric (GC). However, the direct relationship between glucose homeostasis 4-acetylcytosine (ac4C) modification GC remains unclear. Methods: The prognostic value acetyltransferase NAT10 expression was evaluated human cohort. Additionally, preoperative PET/CT data from patients Micro-PET/CT imaging mice were employed assess metabolism. role investigated through various experiments, xenografts, organoids, conditional knockout (cKO) mouse model. underlying mechanisms examined using dot blotting, immunofluorescence staining, co-immunoprecipitation, high-throughput sequencing, among other techniques. Results: Glucose deprivation activates autophagy-lysosome pathway, leading degradation by enhancing its interaction with sequestosome 1 (SQSTM1)/microtubule-associated protein light chain 3 alpha (LC3) complex, ultimately resulting reduction ac4C modification. Furthermore, levels elevated tissues correlate poor prognosis. A strong correlation exists 18F-FDG uptake patients. drives glycolytic metabolism carcinogenesis vitro vivo. Mechanistically, stimulates at intersection coding sequence (CDS) 3' untranslated region (3'UTR) hexokinase 2 (HK2) mRNA, stability activating thereby driving tumorigenesis. Conclusion: Our findings highlight critical crosstalk epitranscriptome carcinogenesis. This finding offers potential strategy targeting NAT10/HK2 axis for treatment patients, especially those highly active

Язык: Английский

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Epigenetic and Immunological Features of Bladder Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 9854 - 9854

Опубликована: Июнь 7, 2023

Bladder cancer (BLCA) is one of the most common types malignant tumors urogenital system in adults. Globally, incidence BLCA more than 500,000 new cases worldwide annually, and every year, number registered increases noticeably. Currently, diagnosis based on cystoscopy cytological examination urine additional laboratory instrumental studies. However, an invasive study, voided cytology has a low level sensitivity, so there clear need to develop reliable markers test systems for detecting disease with high sensitivity specificity. Human body fluids (urine, serum, plasma) are known contain significant amounts tumorigenic nucleic acids, circulating immune cells proinflammatory mediators that can serve as noninvasive biomarkers, particularly useful early detection, follow-up patients, personalization their treatment. The review describes advances epigenetics BLCA.

Язык: Английский

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Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101055 - 101055

Опубликована: Янв. 18, 2024

Язык: Английский

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Novel NF-κB Inhibitor-Conjugated Pt(IV) Prodrug to Enable Cancer Therapy through ROS/ER Stress and Mitochondrial Dysfunction and Overcome Multidrug Resistance

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(8), С. 6218 - 6237

Опубликована: Апрель 4, 2024

Although cisplatin has been widely used for clinical purposes, its application is limited due to obvious side effects. To mitigate the defects of cisplatin, here, six "multitarget prodrugs" were synthesized by linking and NF-κB inhibitors. Notably, complex 9 demonstrated a 63-fold enhancement in activity against A549/CDDP cells with lower toxicity toward normal LO2 compared cisplatin. Additionally, could effectively cause DNA damage, induce mitochondrial dysfunction, generate reactive oxygen species, cell apoptosis through pathway ER stress. Remarkably, inhibited NF-κB/MAPK signaling disrupted PI3K/AKT transduction. Importantly, showed superior vivo antitumor efficiency or combination cisplatin/4, without systemic A549 xenograft models. Our results that dual-acting mechanism endowed complexes high low toxicity, which may represent an efficient strategy cancer therapy.

Язык: Английский

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