RBM15‑mediating MDR1 mRNA m6A methylation regulated by the TGF‑β signaling pathway in paclitaxel‑resistant ovarian cancer

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 63(4)

Published: Aug. 11, 2023

Ovarian cancer (OC) lacks effective biomarkers for diagnosis at an early stage and often develops chemoresistance after the initial treatment advanced stage. RNA‑binding motif protein 15 (RBM15) is RNA m6A methylation mediator that serves oncogenic role in some cancers. However, function molecular mechanisms of RBM15 ovarian tumorigenesis remain to be elucidated. The present study identified overexpression OC tissues paclitaxel (PTX)‑resistant cells using reverse transcription‑quantitative (q)PCR, western blotting immunohistochemistry. Clinical data analyses showed high expression was associated with poor prognosis patients OC. Overexpression led increase cell viability colony formation a decrease sensitivity PTX apoptosis, whereas knockdown resulted inhibition vitro tumor vivo increased apoptosis time‑ dose‑dependent manner. Furthermore, reduced spheroid PTX‑resistant cells. Silencing decreased multidrug resistance 1 (MDR1) mRNA detected by methylated immunoprecipitation‑qPCR assay downregulated chemo‑drug efflux pump MDR1 levels. Finally, suppressed activation TGF‑β signaling pathway. Thus, findings revealed TGF‑β/RBM15/MDR1 regulatory mechanism. Targeting may provide novel therapeutic strategy

Language: Английский

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Targeted anti-angiogenesis therapy for advanced osteosarcoma

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Aug. 26, 2024

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that reevaluation current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis metabolic targets nanomedicine therapy. The tumorigenesis development closely related angiogenesis. therapy crucial treat osteosarcoma; however, recent clinical trials found it insufficient efficacy. solve this problem, causes failure improve should be investigated. This review focuses on summarizing pathophysiological mechanisms angiogenesis advances osteosarcoma. We also discuss some studies, with aim providing new ideas for patients.

Language: Английский

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New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 251, P. 154902 - 154902

Published: Oct. 21, 2023

Language: Английский

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Exonic CircGUCY1A2 Inhibits Pulmonary Artery Smooth Muscle Cells Phenotypic Switching Via Regulating O-glycosylation of COL3A1 in Pulmonary Hypertension

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 992, P. 177328 - 177328

Published: Feb. 4, 2025

Language: Английский

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Glycolysis-related gene signatures and the functional role of P4HA1 in osteosarcoma prognosis

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114492 - 114492

Published: Feb. 1, 2025

Osteosarcoma, a primary malignant bone tumor predominantly affecting children and adolescents, is characterized by aerobic glycolysis, which intricately linked to progression metastasis, yet its prognostic implications remain underexplored. This study aimed develop model utilizing glycolysis-related genes elucidate the functional role of P4HA1, key gene within this model, in osteosarcoma prognosis immune cell infiltration. We collected clinical transcriptomic data from patients UCSC Xena GEO databases. Through univariate Cox LASSO regression analyses, we identified 12 that significantly influence prognosis. These were employed construct risk score accurately predicted patient outcomes as demonstrated survival analysis ROC curves, with an AUC 0.899, 0.881, 0.878 for 1-year, 3-year, 5-year predictions, respectively. The was particularly effective across different subgroups. Immune infiltration revealed CD8+ T cells, naïve CD4+ resting dendritic activated mast cells contributed model's predictive power. also showed significant enrichment immune-related signaling pathways, indicating robust association between status glycolytic-related scores Notably, P4HA1 upregulated tissues promoted proliferation glycolysis-dependent manner, evidenced increased intracellular ATP levels, inhibited glucose absorption, elevated lactate levels P4HA1-overexpressing cells. promotion could be attenuated glycolysis inhibitor 2-DG, highlighting dependency P4HA1's action. In conclusion, developed integrating genes, particular emphasis on P4HA1. Our findings highlight interplay disease provides insights targeted therapies foundation further research into treatment.

Language: Английский

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Review of the role and potential clinical value of m6A methylation modifications in the biological process of osteosarcoma

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Osteosarcoma (OS), an aggressive bone tumor, is a substantial threat to the quality of life and survival affected individuals. Despite recent improvements in OS therapies, considerable variability chemotherapy resistance this cancer necessitate continuous research discover new treatment targets biomarkers. Recent epigenetic advances highlight crucial role N6-methyladenosine (m6A) methylation cancer. In OS, m6A has been demonstrated be pivotal component pathogenesis. This review introduces findings regarding association between regulators summarizes potential clinical applications regulators, including proliferation, growth, apoptosis, cell migration, invasion, metastasis; relationship resistance; prognosis. Our had certain limitations. The interaction other oncogenic factors, such as lncRNAs ncRNAs, not fully understood. We hope that these methods will translated into effective treatment.

Language: Английский

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CircRNAs: a novel potential strategy to treat breast cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Breast cancer is among the most prevalent malignant tumors worldwide, with triple-negative breast (TNBC) being aggressive subtype and lacking effective treatment options. Circular RNAs (circRNAs) are noncoding that play crucial roles in development of tumors, including cancer. This article examines progress research on circRNAs cancer, focusing four main areas: 1) epidemiology, classification, treatment; 2) structure, discovery process, characteristics, formation, functions circRNAs; 3) expression, mechanisms, clinical relevance, recent advances study cells immune microenvironment, particularly TNBC; 4) challenges future prospects use BC research.

Language: Английский

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USP7 promotes the malignant progression of osteosarcoma through the KPNA2/PKLR axis

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111819 - 111819

Published: April 1, 2025

Language: Английский

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Epitranscriptomic Role of m6A in Obesity-Associated Disorders and Cancer Metabolic Reprogramming

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 498 - 498

Published: April 27, 2025

The global rise in obesity and its associated metabolic disorders underscores the need for a deeper investigation into their underlying molecular mechanisms. While genetic factors are well-established contributors, recent research has increasingly focused on epigenetic regulators, particularly N6-methyladenosine (m6A)—the most prevalent internal RNA modification eukaryotes. This post-transcriptional plays crucial role metabolism by regulating mRNA stability, splicing, nuclear export, translation efficiency. Notably, emerging evidence implicates m6A both adipogenesis dysregulation. In this review, we systematically examine three key dimensions: (1) mechanisms of modification, including writers, erasers, readers, obesity; (2) dysregulated patterns obesity-related pathologies, such as type 2 diabetes (T2D), insulin resistance, dysfunction-associated steatotic liver disease (MASLD), glycolysis cancer cells; (3) therapeutic potential targeting regulators. By critically assessing advancements, highlight m6A’s dual sensor modulator, offering novel insights strategies combating syndromes.

Language: Английский

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Identification and experimental validation of key m6A modification regulators as potential biomarkers of osteoporosis

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 6, 2023

Osteoporosis (OP) is a severe systemic bone metabolic disease that occurs worldwide. During the coronavirus pandemic, prioritization of urgent services and delay elective care attenuated routine screening monitoring OP patients. There an need for novel effective diagnostic biomarkers require minimal technical time investments. Several studies have indicated N6-methyladenosine (m6A) regulators play essential roles in diseases, including OP. The aim this study was to identify key m6A as through gene expression data analysis experimental verification. GSE56815 dataset served training 40 women with high mineral density (BMD) low BMD. levels 14 major were analyzed screen differentially expressed two groups. impact modification on metabolism microenvironment characteristics explored, osteoblast-related osteoclast-related sets. Most metabolism-related sets dysregulated low-BMD samples, their relationship also tightly linked. In addition, consensus cluster performed, distinct patterns identified samples. Subsequently, by univariate multivariate logistic regression analyses, we four regulators, namely, METTL16, CBLL1, FTO, YTHDF2. We built model based regulators. CBLL1 YTHDF2 protective factors, whereas METTL16 FTO risk ROC curve test validated had moderate accuracy distinguishing high- Furthermore, regulatory network constructed hub 26 target genes, which enhanced our understanding mechanisms Finally, vivo vitro, consistent bioinformatic results. Our findings are specific value These modules could be used future.

Language: Английский

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