Translational Oncology, Journal Year: 2025, Volume and Issue: 56, P. 102386 - 102386
Published: April 18, 2025
Language: Английский
International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(10), P. 3099 - 3114
Published: Jan. 1, 2023
Background: Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism chemo-resistance remains unclear, and developing available therapies effective biomarkers resistant EOC in urgent demand. Stemness cells directly results chemo-resistance. Exosomal miRNAs rebuild tumor microenvironment (TME) act as widely used clinical liquid biopsy markers. Methods: In our study, high throughput screenings comprehensive analysis were performed to screen miRNAs, which both up-regulated tissues related stemness, miR-6836 was identified accordingly. Results: Clinically, expression closely correlated with chemotherapy response survival patients. Functionally, promoted cell cisplatin by increasing stemness suppressing apoptosis. Mechanistically, targeted DLG2 enhance Yap1 nuclear translocation, regulated TEAD1 forming positive feedback loop: miR-6836-DLG2-Yap1-TEAD1. Furthermore, could be packaged into secreted exosomes cisplatin-resistant exosomal able delivered cisplatin-sensitive reverse their response. Conclusion: Our study revealed mechanisms resistance, possible therapeutic target marker EOC.
Language: Английский
Citations
14
Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(11), P. 2382 - 2392
Published: Oct. 12, 2023
Abstract Receptor for activated C kinase 1 (RACK1) has been confirmed to take part in multiple biological events and the mechanism supporting abnormal RACK1 expression ovarian cancer (OC) remains be characterized. Here, we identified Smad ubiquitin regulatory factor 2 (SMURF2) as a bona fide E3 ligase of OC. SMURF2 effectively added K6, K33 K48 chains RACK1, resulting polyubiquitination instability RACK1. PCAF promoted acetylation at K130, leading SMURF2-mediated ubiquitination inhibited promote OC progression. The levels were negatively correlated. was low human cancer, decreased increased stability, which progression, strongly associated with poor patients’ prognosis. In general, our results demonstrated that plays pivotal role stabilizing turn facilitates tumorigenesis OC, suggesting SMURF2-RACK1 axis may prove potential targets treatment
Language: Английский
Citations
13
Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114551 - 114551
Published: July 26, 2024
Language: Английский
Citations
5
BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)
Published: Jan. 2, 2024
Abstract Background There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases susceptibility individuals to ovarian cancer (OC). However, relationship between DM and OC remains largely unexplored. The objective this study is provide preliminary insights into shared molecular regulatory mechanisms potential biomarkers OC. Methods Multiple datasets from GEO database were utilized for bioinformatics analysis. Single cell analysed. Subsequently, immune infiltration analysis was performed on mRNA expression data. intersection these yielded set common genes associated with both DM. Using overlapping Cytoscape, protein‒protein interaction (PPI) network constructed, 10 core targets selected. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses then conducted targets. Additionally, advanced construct TF-mRNA-miRNA coregulatory based identified Furthermore, immunohistochemistry staining (IHC) real-time quantitative PCR (RT-qPCR) employed validation biological functions proteins, including HSPAA1, HSPA8, SOD1, transcription factors SREBF2 GTAT2, tumors. Results data OC, as well using single-cell datasets, reveals differences mononuclear levels. By intersecting total 119 related cells identified. PPI further hub genesincludingHSP90AA1, SNRPD2, UBA52, RPL13A, RPSA, ITGAM, PPP1CC, PSMA5, Enrichment indicated that are primarily neutrophil degranulation, GDP-dissociation inhibitor activity, IL-17 signaling pathway, suggesting their involvement regulation tumor microenvironment. TF-gene miRNA-gene networks validated NetworkAnalyst. TFs included SREBF2, GATA2, SRF, while miRNAs miR-320a, miR-378a-3p, miR-26a-5p. Simultaneously, IHC RT-qPCR reveal differential tumors after onset diabetes. revealed GATA2 may influence HSP90AA1, SOD1. Conclusion This gene predicted monocytes. Our research findings contribute identifying underlying
Language: Английский
Citations
4
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 320 - 320
Published: Jan. 1, 2025
The mortality rate of ovarian cancer (OC) remains the highest among female gynecological malignancies. Advanced age is risk factor for OC development and progression, yet little known about role aged tumor microenvironment (TME). We conducted RNA sequencing lipidomic analysis young gonadal adipose tissue from rat xenografts before after formation. rates formation (p = 0.047) volume 0.002) were significantly higher in rats than their counterparts. data showed significant differences gene expression profiles between groups tissues < 0.05), including S100a8, S100a9, Il1rl1, Lcn2, C3, Hba-a1, Fcna, Pnpla3. At time generation, there also changes lipid components within rats, with levels free fatty acids (FFAs) triglycerides (TGs) rats. Furthermore, TME immune cell composition, especially inflammation-related cells, neutrophils, myeloid dendritic CD4+ T cells (non-regulatory), mast activation 0.05). correlation neutrophil, omega-5, FFA 18:3 was determined. Additionally, which downregulated inhibited proliferation vitro 0.001). Our study suggests that promotes resulting age-related gene/pathway expression, metabolism, distribution. Targeting aging microenvironment, particularly a promising therapeutic strategy warrants further investigation. Significance: contributes to progression because response regulatory genes S100a8 secreted by adipocytes, preadipocytes, or altering omega-5 metabolism.
Language: Английский
Citations
0
BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 6, 2025
Abstract Ovarian cancer remains the most lethal gynecological malignancy. Despite approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics. New advancements in therapeutic strategies target pivotal hallmarks cancer. This review giving updated overview innovative upcoming therapies treatment ovarian that focuses specific on The constitute a broad concept to reenact complexity malignancies furthermore identify possible targets strategies. For this purpose, we analyzed approvals current clinical phase III studies (registered at ClinicalTrials.gov (National Library Medicine, National Institutes Health; U.S. Department Health Human Services, 2024)) drugs basis their mechanisms action identified approaches. A spectrum currently under investigation targeting mainly “self-sufficiency growth signals,” “genomic instability,” “angiogenesis.” benefit immune checkpoint inhibitors been demonstrated first time. Besides, tumor microenvironment growing interest. Replicative immortality, energy metabolism, promoting inflammation, microbiome are still barely by drugs. Nevertheless, precision medicine, which disease characteristics, becoming increasingly important treatment. Graphical
Language: Английский
Citations
0
Advances in Oncology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 4, 2025
Ovarian cancer has a high mortality rate, primarily due to late diagnosis and complex pathogenesis. This study develops an integrative prognostic model combining genetic, clinical, immunological data predict outcomes in ovarian patients. Utilizing from The Cancer Genome Atlas (TCGA), we identified significant genes through differential expression survival analysis, integrating these with clinical features immune landscape assessments including cell infiltration checkpoint expression. risk score effectively predicted patient survival, distinguishing between low-risk groups outcome differences. High-risk patients demonstrated poor prognosis, greater expression, higher tumor mutational burdens (TMB), suggesting potential responsiveness immunotherapy. model's predictive capacity was validated across multiple cohorts, showing consistent performance prediction treatment response. Calibration curves decision curve analysis confirmed the utility. highlights of integrated approach enhance personalized strategies cancer, aiming improve management outcomes.
Language: Английский
Citations
0
European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)
Published: March 4, 2025
As one member of the Forkhead Box transcription factor, J2 (FOXJ2) is involved in diverse cancers. At present, specific role and mechanism FOXJ2 ovarian cancer (OC) have not been fully addressed, which allows us to fill blank. Accordingly, expression OC cells epithelial was quantified via real-time qPCR. Following transfection, cell counting kit-8, Transwell, wound healing flow cytometry assays were performed measure proliferation, metastasis, apoptosis cycle A2780 HEY. Further, qPCR Western blotting both employed for quantification on levels as well phosphoinositide 3-kinase (PI3K) protein kinase B (AKT) (in unphosphorylated phosphorylated forms). Based results, highly-expressed (P < 0.05). Silencing resulted attenuated reduced numbers migrating invading cells, decreased apoptotic capacity, arrest G1/S phase In addition, knockdown caused downward trend phosphorylation level PI3K AKT The silencing could repress growth metastasis potentials cause vitro, possibly achieved targeting PI3K/AKT pathway.
Language: Английский
Citations
0
Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 403 - 403
Published: March 10, 2025
The tumor microenvironment is a dynamic and complex three-dimensional network comprising the extracellular matrix diverse non-cancerous cells, including fibroblasts, adipocytes, endothelial cells various immune (lymphocytes T B, NK dendritic monocytes/macrophages, myeloid-derived suppressor innate lymphoid cells). A constantly rapidly growing number of studies highlight critical role these in shaping cancer survival, metastatic potential therapy resistance. This review provides synthesis current knowledge on modulating cellular progression response to treatment.
Language: Английский
Citations
0