PUS7‐dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(8)

Опубликована: Авг. 1, 2024

Abstract Background RNA pseudouridylation is a critical post‐transcriptional modification that influences gene expression and impacts various biological functions. Despite its significance, the role of mRNA in cancer remains poorly understood. This study investigates impact pseudouridine synthase 7 (PUS7)‐mediated Alpha‐ketoglutarate‐dependent Dioxygenase alkB Homolog 3 ( ALKBH3 ) gastric cancer. Methods Immunohistochemistry Western blotting were used to assess PUS7 protein levels human tissues. The relationship between progression was examined using 3D colony formation assays subcutaneous xenograft models. Real‐time quantitative PCR (RT‐qPCR), blotting, polysome profiling conducted investigate how regulates ALKBH3. A locus‐specific (Ψ) detection assay identify Ψ sites on mRNA. Results Our findings indicate significant reduction tissues compared adjacent non‐tumour Functional analyses reveal inhibits cell proliferation tumour growth via catalytic activity. Additionally, enhances translation efficiency by modifying U696 site with pseudouridine, thereby attenuating growth. Importantly, functions as suppressor cancer, closely correlated Conclusions PUS7‐dependent translation, suppressing progression. These highlight potential significance biology suggest therapeutic target for Highlights through activity mRNA, inhibiting tumourigenesis. are significantly tumours, which may be prognostic predictors targets patients

Язык: Английский

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Integrative single-cell and multi-omics analyses reveal ferroptosis-associated gene expression and immune microenvironment heterogeneity in gastric cancer

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 17, 2025

Gastric cancer (GC), a prevalent malignancy worldwide, encompasses multitude of biological processes in its progression. Recently, ferroptosis, novel mode cell demise, has become focal point research. The microenvironment gastric is composed diverse populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood. Our study employed single-cell RNA sequencing to thoroughly investigate transcriptomic identify differential cancer, offering fresh insights into cellular diversity underlying molecular mechanisms this disease. We discovered set significantly differentially expressed genes GC, which may serve as valuable leads for future functional investigations. Subsequent analyses, including intersection enrichment, pinpointed implicated conducted comprehensive Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses elucidate roles. In selection model validation section, critical were identified using machine learning algorithms, constructing high predictive accuracy. Besides, distorted immune landscapes further RBL ssGSEA analysis such that complex features interaction networks infiltration by various types cells can be more clearly Correlation different subtypes showed CTSB an important regulator distributions infiltrating cells. Single-cell was utilized map composition microenvironment, provide information elucidating heterogeneity tumor regulation GC. Moreover, distribution FTH1, ZFP36 CIRBP at levels show new research prospects these promoters microenvironment. summary, present augments our knowledge tumorigenesisa scientific basis identifing targets biomarkers therapeutic diagnosis.

Язык: Английский

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Deciphering the pseudouridine nucleobase modification in human diseases: From molecular mechanisms to clinical perspectives

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Язык: Английский

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Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression

Advanced Science, Год журнала: 2024, Номер 11(44)

Опубликована: Окт. 8, 2024

Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing stability, functionality, interactions. To date, over 170 distinct modifications more than 100 enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has made in understanding modification, the regulatory mechanisms that govern proteins themselves remain insufficiently explored. Post‐translational (PTMs) such phosphorylation, ubiquitination, acetylation are crucial modulating function behavior of proteins. However, full extent PTM influence on their role disease development remains to be fully elucidated. This review addresses gaps offering a comprehensive analysis roles PTMs play regulating Mechanistic insights provided into how alter biological processes, contribute cellular function, drive progression. In addition, current landscape is examined, highlighting therapeutic potential targeting for precision medicine. By advancing networks, this seeks facilitate effective strategies inspire future critical area

Язык: Английский

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ALKBH3-mediated m1A demethylation promotes the malignant progression of acute myeloid leukemia by regulating ferroptosis through the upregulation of ATF4 expression

Hematology, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 13, 2025

To investigate the role of ALKBH3 in acute myeloid leukemia (AML), we constructed an animal model xenotransplantation AML. Our study demonstrated that ALKBH3-mediated m1A demethylation inhibits ferroptosis KG-1 cells by increasing ATF4 expression, thus promoting development These findings suggest reducing expression may be a potential strategy to mitigate AML progression.

Язык: Английский

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TOM1L1 mediated the sort of tumor suppressive miR-378a-3p into exosomes and the excretion out of cells to promote ESCC progression

Cancer Gene Therapy, Год журнала: 2025, Номер unknown

Опубликована: Март 23, 2025

Язык: Английский

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TRUB1 is a novel biomarker for promoting malignancy in colorectal cancer via NFκB signaling

Gastroenterology report, Год журнала: 2025, Номер 13

Опубликована: Янв. 1, 2025

Abstract Background Colorectal cancer (CRC) is one of the most aggressive malignancies digestive tract, characterized by aberrant post-transcriptional RNA modifications, including pseudouridine (Ψ). TruB synthase family member 1 (TRUB1) a key but its role in CRC progression remains unclear. Methods Public databases and cell lines were analysed to assess TRUB1 expression CRC. Receiver-operating characteristic (ROC) curve analysis survival performed evaluate diagnostic prognostic significance TRUB1. The impact on tumor proliferation Ψ modification was examined TRUB1-knock-down HCT116 lines. Mechanistically, sequencing control cells conducted identify potential pathways, which validated using real-time polymerase chain reaction (PCR), Western blot, immunofluorescence assays. Results significantly upregulated tissues ROC showed that had strong overexpression associated with poorer overall patients. In cells, apoptosis increased growth slowed nude mice, corresponding increase apoptosis-related proteins decreased modification. indicated necrosis factor α signaling via nuclear kappa B (NFκB) pathway activated cells. Further identified Baculoviral inhibitor repeat-containing 3 (BIRC3) as downstream target gene regulated NFκB pathway. Conclusions serves biomarker for diagnosis prognosis, it can inhibit BIRC3-mediated signaling.

Язык: Английский

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Dual‐Mode Detection of RNA Demethylation Protein ALKBH3 Using a Two‐Legged DNA‐Walker‐Mediated BiOI/In₂O₃‐Gated Organic Photoelectrochemical Transistor Biosensor

Small, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Abstract Organic photoelectrochemical transistor (OPECT) biosensors have emerged as prevalent candidates for bioanalytical technologies because of their intrinsic amplification properties and excellent detection performance. Herein, a novel OPECT biosensor analyzing the RNA demethylation protein ALKBH3 is developed. A BiOI/In 2 O 3 type‐II heterojunction employed photoactive material gate, an organic semiconductor, poly(3,4‐ethylenedioxythiophene): poly(styrenesulfonic) (PEDOT:PSS), used channel modification material. ALKBH3‐mediated demethylation, switch, triggered trans‐cleavage activity CRISPR‐Cas12a system, which subsequently leads to failure in formation bipedal DNA walker. Contrarily, ferrocenecarboxylic acid (FcA), acts effective electron donor, cannot be captured, leading modulation gating characteristics degradation current response. Compared conventional method, exhibits higher sensitivity lower limit protein, thereby facilitating monitoring changes under effect environmental pollutants demonstrating crucial biomarker potential evaluating its toxicological effects.

Язык: Английский

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Pseudouridine synthase 7 (PUS7) affects the prognosis and immune modulation of patients with bladder cancer

Asian Journal of Surgery, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Advancements in pseudouridine modifying enzyme and cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Дек. 16, 2024

Pseudouridine (Ψ) is a post-transcriptional modifier of RNA, often referred to as the 'fifth nucleotide' owing its regulatory role in various biological functions well because significant involvement pathogenesis human cancer. In recent years, research has revealed Ψ modifications different RNA types, including messenger transfer ribosomal small nuclear and long noncoding RNA. Pseudouridylation can significantly alter structure thermodynamic stability, Ψ-adenine (A) base pair more stable than typical uridine (U)-A due structural similarity adenine. Studies have linked expression development progression several digestive system cancers, such liver cancer colorectal cancer, nondigestive breast non-small cell lung prostate glioblastoma, ovarian oral squamous carcinoma, pituitary The present review briefly outlines chemical structure, synthesis, mechanisms Ψ. This summarizes effects pseudouridylation on substrates discusses methods for detecting Last, it focuses how influences emphasizing search novel approaches diagnosis, treatment, prognosis through modification.

Язык: Английский

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