Targeting RNA splicing modulation: new perspectives for anticancer strategy?

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 30, 2025

Language: Английский

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MANF overexpression ameliorates oxidative stress-induced apoptosis of human nucleus pulposus cells by facilitating mitophagy through promoting MFN2 expression

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Language: Английский

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Thymoquinone and Metabolic Reprogramming in Breast Cancer: A New Dimension From Proteomic Analysis

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

ABSTRACT Thymoquinone (TQ) has shown antitumorigenic effects in breast cancer; however, its detailed impact on cell signaling mechanisms requires further investigation. This study aims to elucidate the molecular behind TQ's antiproliferative cancer by analyzing proteome‐level changes. MCF‐7 cells were treated with 15 µM TQ, inhibitory concentration (IC50), for 48 h. Proteins from and untreated (control) groups isolated subjected liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomic analysis. Identified proteins functionally annotated, hub identified using Cytoscape software, verification conducted through Western blot Label‐free quantitation 629 master proteins, 104 upregulated 477 downregulated TQ‐treated samples compared controls. Among these, 150 showed dramatic regulation, including 11 139 ribosomal emerging as central. The heatmap demonstrated robust clustering of replicates. Functional annotations indicated that TQ significantly impacts crucial such carbon metabolism, amino acid biosynthesis, protein synthesis, citrate cycle, essential metabolic reprogramming. identifies novel targets associated reprogramming, previously underexplored effects, highlighting their pivotal role anticancer cancer. These findings could lay groundwork developing future TQ‐based therapies.

Language: Английский

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PROTACs coupled with oligonucleotides to tackle the undruggable

Bioanalysis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 3, 2025

Undruggable targets account for roughly 85% of human disease-related and represent a category therapeutic that are difficult to tackle with traditional methods, but their considerable clinical importance. These generally defined by planar functional interfaces the absence efficient ligand-binding pockets, making them unattainable conventional pharmaceutical strategies. The advent oligonucleotide-based proteolysis-targeting chimeras (PROTACs) has instilled renewed optimism in addressing these challenges. PROTACs facilitate targeted degradation undruggable entities, including transcription factors (TFs) RNA-binding proteins (RBPs), via proteasome-dependent mechanisms, thereby presenting novel approaches diseases linked targets. This review offers an in-depth examination recent progress integration PROTAC technology oligonucleotides target traditionally proteins, emphasizing design principles mechanisms action innovative PROTACs.

Language: Английский

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Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155864 - 155864

Published: March 1, 2025

Language: Английский

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RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 5, 2025

RNA-binding proteins (RBPs) are pivotal mediators of the alternative splicing (AS) machinery pre-mRNA. Research has demonstrated that AS process is significantly dysregulated and plays a crucial role in bladder cancer (BLCA). We conducted comprehensive screening analysis TCGA-BLCA cohort, specifically focusing on genes with significant differences expression levels between carcinoma adjacent non-cancerous tissues. Among 500 differentially expressed genes, 5 were identified. Only protein multiple (RBPMS) consistent downregulation BLCA was correlated an unfavorable prognosis for affected patients. Subsequent experiments revealed RBPMS exerted inhibitory effects epithelial-mesenchymal transition (EMT) pathway migratory potential cells. RNA-Seq identified ANKRD10 as key target mRNA regulated by BLCA. depletion cells resulted increased ANKRD10-2 expression. functioned transcriptional co-activator MYC proteins, thereby augmenting their activity. Furthermore, knockdown rescued migration enhancement induced Taken together, this study mechanism whereby suppresses invasion attenuating activity via ANKRD10.

Language: Английский

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SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid–liquid phase separation to promote oral cancer progression

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Oral cancer represents a significant proportion of head and neck malignancies, accounting for approximately 3 % all malignant tumors worldwide. Alternative splicing (AS), post-transcriptional regulatory mechanism, is increasingly linked to development. The precise impact AS on oral progression not well understood. Bioinformatics, semi-quantitative RT-PCR, minigene reporter system detect the skipping SLC37A4 exon 7 in cancer. FRAP, live cell immunofluorescence demonstrates that SRSF9 can undergo liquid-liquid phase separation (LLPS). In vivo vitro experiments with subcutaneous graft tumors, CCK8, EdU, transwell, others were used effects its induced SLC37A4-S isoforms phenotype cells. Our investigation revealed multitude aberrant alternative events within tumor tissues, most notably pronounced gene. This anomaly leads production truncated isoform, SLC37A4-S, which associated poor prognosis significantly augments proliferation metastatic potential cells relative wild-type SLC37A4-L. Mechanically, may play role SLC37A4. Furthermore, capable undergoing LLPS, process driven by arginine-serine-rich (RS) domain. Disruption LLPS through use inhibitors or mutants effectively prevents influence Significantly, our research both regulated contribute cisplatin chemotherapy resistance study elucidates mechanism mediates cancer, thereby establishing basis considering as therapeutic targets treatment.

Language: Английский

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ZBP1 senses splicing aberration through Z-RNA to promote cell death

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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PTBP3 Mediates IL‐18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 8, 2024

Gallbladder cancer (GBC) is the most common malignant tumor of biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated development a variety tumors. Combining GEO database and GBC mRNA-seq analysis, it found high expression factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping interleukin-18 (IL-18), resulting ΔIL-18, an isoform specifically expressed That ΔIL-18 promotes immune escape by down-regulating FBXO38 transcription levels CD8+T cells reduce PD-1 ubiquitin-mediated degradation revealed. Using HuPBMC mouse model, role promoting growth confirmed, showed antisense oligonucleotide blocked production displayed anti-tumor activity. Furthermore, H3K36me3 IL-18 recruiting via MRG15 demonstrated, thereby coupling processes splicing. Interestingly, also H3K36 methyltransferase SETD2 binds hnRNPL, interfering pre-mRNA. Overall, this study provides new insights into how aberrant mechanisms affect escape, potential perspectives for improving immunotherapy.

Language: Английский

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Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 28, 2024

Language: Английский

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