Tianli Mu, Bo Ren, Ziteng Kuang, Runze He, Bingjie Rui, Ye Yang, Yuxi Liu, Danbo Geng, Yuci Zhang, Min Wang
{"title":"Mechanism by which SUGT1 downregulates FH to promote proliferation and migration in serous ovarian cancer.","authors":"Tianli Mu, Bo Ren, Ziteng Kuang, Runze He, Bingjie Rui, Ye Yang, Yuxi Liu, Danbo Geng, Yuci Zhang, Min Wang","doi":"10.1186/s13048-025-01744-w","DOIUrl":"10.1186/s13048-025-01744-w","url":null,"abstract":"<p><strong>Background: </strong>SUGT1 (Suppressor of the G2 allele of SKP1) and FH (fumarate hydratase) have recently garnered significant attention from the research community. SUGT1 functions as a molecular chaperone, regulating the stability and activity of various proteins, while FH is a key enzyme in the tricarboxylic acid cycle, catalyzing the reversible conversion of fumarate to malate. Existing literature has established their essential roles in signaling, tumorigenesis, and cancer progression. However, their functions and mechanisms in ovarian cancer (OC) remain poorly understood.</p><p><strong>Results: </strong>We found that high SUGT1 expression is associated with a more advanced FIGO stage in OC. SUGT1 knockdown significantly inhibits OC cell proliferation and metastasis, while its overexpression has the opposite oncogenic effect. Mechanistically, we revealed that SUGT1 promotes FH protein degradation via the ubiquitin-proteasome pathway. Moreover, FH knockdown partly reversed the inhibitory effects of SUGT1 knockdown on tumor cell proliferation, migration, and proteins of phosphorylated PI3K/AKT and Vimentin. In summary, We demonstrated that SUGT1 exerts oncogenic functions in OC by regulating FH stability.</p><p><strong>Conclusions: </strong>Our study is the first to provide experimental evidence elucidating the SUGT1-FH relation and its role in OC progression, offering potential significance for clinical diagnosis and therapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"168"},"PeriodicalIF":4.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Munachiso Iheme Ndukwe, Matteo Pavone, Dominik Habes, Nicolo Bizzarri, Martin Stepan, Petra Bretová, Floriana Mascilini, Dominik Karasek, Denisa Pohankova, Akaninyene Ubom, Jana Marie Havigerova, Jiri Haviger, Igor Sirak
{"title":"The role of ultrasound-guided tru-cut biopsy in ovarian cancer: a systematic review of its safety, adequacy, and accuracy with meta-analysis of diagnostic performance.","authors":"Munachiso Iheme Ndukwe, Matteo Pavone, Dominik Habes, Nicolo Bizzarri, Martin Stepan, Petra Bretová, Floriana Mascilini, Dominik Karasek, Denisa Pohankova, Akaninyene Ubom, Jana Marie Havigerova, Jiri Haviger, Igor Sirak","doi":"10.1186/s13048-025-01739-7","DOIUrl":"10.1186/s13048-025-01739-7","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the safety, adequacy and accuracy of ultrasound-guided tru-cut biopsy in the diagnosis of ovarian cancer.</p><p><strong>Methods: </strong>A systematic search of PubMed, Web of Science, and Scopus was conducted through June 2024. Studies meeting predefined criteria were included in the review. The quality of diagnostic accuracy studies was assessed using QUADAS-2. A meta-analysis was performed on studies reporting complete 2 × 2 diagnostic data.</p><p><strong>Results: </strong>A total of 2,250 articles were initially screened, and after the removal of duplicates, 54 articles were deemed eligible for full-text assessment. Ultimately, 18 studies, comprising 1,867 patients who underwent ultrasound-guided tru-cut biopsy, were included in the systematic review. A total of 16 complications were reported across 1,898 biopsies performed in the included studies, resulting in a mean complication rate of 0.58% (95% CI: 0.187- 0.964%). Adequacy for histological and immunohistochemical examination after one attempt was reported in 16 studies, with a mean adequacy rate of 95.1% (95% CI: 92.69- 97.50%) and a median rate of 95.97%. Diagnostic accuracy was assessed in 13 studies, revealing a mean diagnostic accuracy of 95.54% (95% CI: 93.19- 97.89%) and a median of 97.48%.In the meta-analysis of 10 studies, pooled sensitivity was 98.6%, specificity 41.9%, positive predictive value (PPV) 99.0%, and negative predictive value (NPV) 47.2%, with high heterogeneity observed in specificity and NPV estimates.</p><p><strong>Conclusions: </strong>Ultrasound guided tru-cut biopsy is a safe and effective diagnostic method, demonstrating a high adequacy rate for histological and immunohistochemical analysis. It shows excellent performance in confirming malignancy and supports preoperative decision making. To further define its role in the diagnostic pathway for ovarian cancer, additional prospective multicenter studies are needed-both to validate its reliability in negative cases and to ensure tissue adequacy for advanced molecular testing in the context of personalized medicine.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"166"},"PeriodicalIF":4.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SLC4A11 is a targetable marker correlated with therapeutic responses in ovarian cancer.","authors":"Xin Li, Jia Yuan, Fanchen Wang, Bin Guan, Wencai Guan, Jimin Shi, Qi Lu, Jihong Zhang, Guoxiong Xu","doi":"10.1186/s13048-025-01758-4","DOIUrl":"10.1186/s13048-025-01758-4","url":null,"abstract":"<p><strong>Background: </strong>Solute carrier family 4 member 11 (SLC4A11) is involved in borate homeostasis, metabolism reprogramming, cell growth, and cell adhesion. However, the biological function of SLC4A11 in ovarian cancer (OC) is still unclear. This study explores the anti-tumor and biological activities of SLC4A11 in OC.</p><p><strong>Methods: </strong>The expression and function of SLC4A11 were evaluated in human OC cells and xenograft mice. SLC4A11 expression was evaluated using data from the TCGA-OV, GTEx, and GEO datasets. The genetic status of SLC4A11 was analyzed by the cBioPortal database. The data of expressional abundance, immunochemistry, and immunofluorescence were analyzed through the HPA database. The correlation between SLC4A11 and immune responses was analyzed with the CIBERSORT database, whereas therapeutic responses were analyzed with the CellMiner database.</p><p><strong>Results: </strong>SLC4A11 was found to be highly expressed in OC tissues/cells and had a relationship with an unfavorable prognosis in patients with OC. The overexpressed SLC4A11 promoted OC cell proliferation, migration, and invasion. Reducing SLC4A11 caused the cell cycle arrest at the G0/G1 phase and triggered apoptosis. The in vivo study with a xenographic model revealed that the knockdown of SLC4A11 suppressed tumor growth. Subsequent bioinformatics analyses revealed that SLC4A11 expression was associated with immune responses and therapeutic drug sensitivity.</p><p><strong>Conclusions: </strong>These findings have illustrated the oncogenic role of SLC4A11 in OC. SLC4A11 is overexpressed and is correlated with poor prognosis in OC. SLC4A11 may be a targetable biomarker and has a potential value of application in treating patients with OC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"167"},"PeriodicalIF":4.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Verhaeghe, K J Lindquist, M E Bleil, M Rosen, R F Redberg, D Haisenleder, C E McCulloch, Marcelle I Cedars
{"title":"Ovarian aging, cardiovascular risk and inflammation: insights from the OVA study.","authors":"C Verhaeghe, K J Lindquist, M E Bleil, M Rosen, R F Redberg, D Haisenleder, C E McCulloch, Marcelle I Cedars","doi":"10.1186/s13048-025-01754-8","DOIUrl":"10.1186/s13048-025-01754-8","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease is the leading cause of death among women and is associated with both metabolic syndrome and ovarian aging. Chronic inflammation has been proposed as a potential common underlying mechanism linking these conditions. This study aimed to examine the associations between inflammatory markers (interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein) and metabolic syndrome, with markers of ovarian aging and cardiovascular risk.</p><p><strong>Results: </strong>In the cross-sectional analysis of 829 women aged 25-45, no significant associations were found between inflammatory markers, metabolic syndrome, and ovarian aging measures (anti-Müllerian hormone [AMH] and antral follicle count [AFC]), except for a modest association between metabolic syndrome and AMH (mean difference 0.085; 95% CI: 0.035 to 0.134). Similarly, inflammatory markers and metabolic syndrome were not significantly associated with the Framingham Risk Score. In the longitudinal analysis of 307 participants, changes in AMH and AFC were not associated with inflammatory markers or metabolic syndrome. However, higher levels of IL-6 and TNF-α were associated with the Framingham Risk Score, whereas hsCRP and metabolic syndrome were not.</p><p><strong>Conclusion: </strong>These findings do not support the hypothesis that inflammation is a central mechanism linking ovarian aging to cardiovascular risk. The absence of consistent associations across analyses suggests that alternative pathways may underlie this relationship. Further research incorporating a broader range of biomarkers is warranted to elucidate the complex interactions between reproductive aging and cardiovascular health in women.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"164"},"PeriodicalIF":4.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"hnRNPA2B1 restrains granulosa cell ferroptosis by m<sup>6</sup>A/SLC7A11 in premature ovarian failure.","authors":"Jing Xiong, Ling He, Yongjing Zhang, Xing Zhao","doi":"10.1186/s13048-025-01718-y","DOIUrl":"10.1186/s13048-025-01718-y","url":null,"abstract":"<p><p>Premature ovarian failure (POF) is a relatively severe gynecological disorder that is often accompanied by other systemic diseases. Here, this study identified that N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) key enzyme heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) was associated with POF pathophysiological process. In the chemotherapy induced POF animal and cells, hnRNPA2B1 was down-regulated upon cisplatin (CDDP) treatment. Functionally, hnRNPA2B1 inhibited the ferroptosis phenotype by m<sup>6</sup>A/SLC7A11 of granulosa cells. Moreover, hnRNPA2B1 up-regulated the autophagy by inhibiting PI3K/AKT/mTOR pathway of granulosa cells. Besides, rescue experiments confirmed that hnRNPA2B1/SLC7A11 axis repressed the ferroptosis of granulosa cells through m<sup>6</sup>A-dependent manner. In summary, the research identified the critical role of hnRNPA2B1 in granulosa cells ferroptosis, which provides novel insight for POF treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"165"},"PeriodicalIF":4.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The association between triglyceride-glucose index and polycystic ovary syndrome: a systematic review and meta-analysis across different populations.","authors":"Amin Javidan, Alireza Azarboo, Sayeh Jalali, Parisa Fallahtafti, Shabboo Moayyed, Marjan Ghaemi, Azadeh Tarafdari, Sedigheh Hantoushzade","doi":"10.1186/s13048-025-01717-z","DOIUrl":"10.1186/s13048-025-01717-z","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age. The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistence, has gained attention for its simplicity and diagnostic accuracy across metabolic disorders. This study aims to assess the association of the TyG index with PCOS.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science were searched up to December 2024. Observational studies reporting TyG indices in PCOS and control groups were included. Subgroup and meta-regression analyses explored sources of heterogeneity. Sensitivity analysis and publication bias assessments ensured robustness.</p><p><strong>Results: </strong>Fifteen studies (7,175 participants) were analyzed. The TyG index was significantly higher in women with PCOS compared to non-PCOS controls (SMD 0.34, 95% CI 0.14-0.54). Subgroup analysis revealed a significant association in Chinese studies (SMD 0.42, 95% CI 0.35-0.49) and cross-sectional studies (SMD 0.45, 95% CI 0.32-0.57). The TyG index exhibited excellent diagnostic accuracy for distinguishing PCOS patients with metabolic syndrome (AUC 0.91, 95% CI 0.85-0.96). Similarly, the TyG-BMI index showed a significant association with PCOS (SMD 0.34, 95% CI 0.10-0.57) and considerable diagnostic performance for insulin resistance in PCOS population (AUC 0.81, 95% CI 0.75-0.88). Meta-regression analysis identified no significant impact of age, body mass index (BMI), or lipid profiles on heterogeneity.</p><p><strong>Conclusions: </strong>The TyG index demonstrates strong potential for PCOS screening, though cut-off values require further validation and accuracy may differ across populations.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"163"},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ramya Nair, Prachi Agarwal, Mrunmayi Ashish Gadre, Kirthanshri S Vasanthan, Raviraja N Seetharam
{"title":"Stem cell treatments for female reproductive disorders: a comprehensive review.","authors":"Ramya Nair, Prachi Agarwal, Mrunmayi Ashish Gadre, Kirthanshri S Vasanthan, Raviraja N Seetharam","doi":"10.1186/s13048-025-01750-y","DOIUrl":"10.1186/s13048-025-01750-y","url":null,"abstract":"<p><p>Stem cell research is advancing rapidly, offering substantial promise in reproductive medicine, particularly in addressing infertility and other reproductive disorders. Although recent advances have generated significant interest, the successful translation of stem cell treatments from preclinical research settings to clinical practice requires a comprehensive understanding of the underlying mechanisms and methodological approaches. This review assesses the current state of stem cell applications in the field of reproductive medicine, emphasizing current research and development, as well as the associated challenges. Adult stem cell-based interventions show considerable potential for treating reproductive tract disorders, mainly ovarian and endometrial regeneration. Despite these promising developments, the transition to widespread clinical implementation is hampered by several challenges, including its heavy reliance on preclinical animal data. The promise of stem cell therapy is considerable, however, validated mechanisms need to be developed that can fully harness their therapeutic capabilities in clinical settings. This review consolidates and evaluates the evidence regarding the therapeutic potential of various stem cell sources, emphasizing their benefits and drawbacks. Although stem zcell therapies have substantial potential for rejuvenating organ dysfunction, future research studies should focus on defining methodological enhancements, such as improving stem cell delivery methods and ensuring long-term safety, to overcome current limitations.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"161"},"PeriodicalIF":4.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Xinyan, Yu Ting, Zhang Xi, He Shangfan, Li Junwei, Zhu Jiaqiao, Ju Huiming, Li Feng, Xue Tongmin
{"title":"Exercise-diet intervention ameliorates but fails to fully reverse obesity-induced ovarian dysfunction: evidence spanning folliculogenesis to embryonic development.","authors":"Chen Xinyan, Yu Ting, Zhang Xi, He Shangfan, Li Junwei, Zhu Jiaqiao, Ju Huiming, Li Feng, Xue Tongmin","doi":"10.1186/s13048-025-01748-6","DOIUrl":"10.1186/s13048-025-01748-6","url":null,"abstract":"<p><p>Obesity, a globally prevalent chronic disease, disrupts systemic homeostasis and impairs female fertility, yet the mechanisms linking adipose dysfunction to ovarian reserve remain unclear. Using high-fat diet-induced obese C57BL/6 mouse models (HFD) and exercise-diet intervention models (SE group), we systematically evaluated obesity-associated reproductive deficits. Histomorphological analysis revealed that HFD mice exhibited ovarian atrophy, increased atretic follicles, and reduced primordial/antral follicle counts, which were partially restored by SE intervention. TEM demonstrated lipid droplet accumulation and mitochondrial heterogeneity in HFD ovaries, with residual vacuolization persisting despite SE-mediated improvement. Superovulation assays demonstrated reduced oocyte production in HFD mice, accompanied by impaired in vivo maturation and blastocyst formation. Immunofluorescence revealed abnormal spindle assembly and heterogeneous mitochondrial distribution in HFD oocytes, potentially associated with elevated ROS. Mechanistically, HFD downregulated folliculogenesis regulators (BMP-15, HIF-1α, PTEN/AKT/FoxO3) while upregulating metabolic stress markers (Chemerin, CMKLR1). Western blot confirmed reduced ovarian protein acetylation and BMP-15/HIF-1α expression in HFD mice, with partial recovery following exercise-diet intervention. These findings demonstrate obesity-induced dual impairments: mitochondrial-ROS dysfunction compromising oocyte competence and BMP-15/HIF-1α suppression disrupting follicular survival through PTEN-AKT-FoxO3 signaling. Although exercise-diet intervention improved metabolic parameters and oocyte quality, residual abnormalities highlighted irreversible impairments. Our study identifies obesity as a driver of ovarian aging and emphasizes the fertility-enhancing potential of combined exercise-diet intervention in obese female mice.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"160"},"PeriodicalIF":4.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Zhang, Guiyun Cheng, Wenwen Jiang, Beihua Kong, Shu Yao, Xihan Liu
{"title":"5-methylcytosine regulated CCNL2 promotes tumorigenesis and cisplatin resistance of ovarian cancer with therapeutic implications.","authors":"Kai Zhang, Guiyun Cheng, Wenwen Jiang, Beihua Kong, Shu Yao, Xihan Liu","doi":"10.1186/s13048-025-01753-9","DOIUrl":"10.1186/s13048-025-01753-9","url":null,"abstract":"<p><strong>Backgroud: </strong>Ovarian cancer (OC) is the most lethal gynecological tumor, primarily due to resistance to chemotherapy. Cyclin L2 (CCNL2) is a novel member of the cyclin family and mainly localized in nucleus. It regulates transcription and alternative splicing by interacting with cyclin-dependent kinases. However, its role in OC chemoresistance remains unknown.</p><p><strong>Results: </strong>Here, we demonstrated that the expression level of CCNL2 was higher in OC tissues as well as in various other tumor types. Furthermore, elevated expression of CCNL2 indicated a poor prognosis in ovarian cancer. Functionally, CCNL2 promoted OC cell proliferation and xenograft growth. Depletion of CCNL2 enhanced chemotherapy sensitivity in OC cells. Mechanistically, YBX1 directly bound to CCNL2 mRNA, and its depletion reduced CCNL2 mRNA stability and protein expression. MeRIP assays revealed that YBX1 regulated CCNL2 via 5-methylcytosine (m⁵C) modification. Mutation of the key residue of YBX1 required for m<sup>5</sup>C function led to decreased CCNL2 expression. Further investigation of the YBX1 regulatory network identified a direct interaction between YBX1 and MATR3, which cooperatively modulated downstream targets. Notably, MATR3 knockdown reversed the YBX1-induced upregulation of CCNL2. Virtual screening identified YB-B1 as a YBX1 inhibitor that effectively downregulated both YBX1 and CCNL2 expression. In vitro, YB-B1 suppressed ovarian cancer cell proliferation and enhanced cisplatin cytotoxicity. Furthermore, patient-derived tumor xenograft (PDX) model also confirmed its chemosensitizing effect.</p><p><strong>Conclusions: </strong>In summary, we demonstrated that CCNL2 promoted OC cell proliferation and chemoresistance, with its expression regulated by YBX1 via m<sup>5</sup>C methylation. The small molecule inhibitor YB-B1 was identified as a promising solution to overcome chemotherapy resistance.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"162"},"PeriodicalIF":4.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of high-grade serous ovarian cancer stem cell-based subtypes and prognostic model and identification of highly expressed VSIG4 and STAB1 in macrophages.","authors":"Huijuan Wu, Dan Li, Lu Sun, Hualin Song, Ke Wang","doi":"10.1186/s13048-025-01747-7","DOIUrl":"10.1186/s13048-025-01747-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells are associated with tumorigenesis, aggression, and drug resistance. We aimed to identify stem cell-related subtypes and a prognostic tool, and to investigate potential stem cell-related genes contributing to high-grade serous ovarian cancer (HGSOC).</p><p><strong>Methods: </strong>Stem cell pathways were used to determine tumor subtypes and the least absolute shrinkage and selection operator regression was conducted to construct a prognostic risk model, with robustness validation in external datasets. We assessed immune characteristics and therapeutic responses of risk score. Macrophage subpopulations were identified using single cell data, and pseudo-time analysis revealed the changes of macrophages during cell state transition.</p><p><strong>Results: </strong>HGSOC patients were stratified into stem cell pathway-related clusters (C1, C2) and stem cell-related clusters (GC1, GC2). Patients in C1 and GC1 exhibited better prognosis, increased ImmuneScore, decreased TumorPurity and low immune escape. Patients in C1 were sensitive to gemcitabine while patients in GC1 were sensitive to cisplatin, cyclophosphamide, gemcitabine and niraparib. Risk score was constructed based on 15 genes (IL2RG, STAB1, C2, CD163, FBXO17, VSIG4, CXCL11, CXCL13, GJB1, GPC3, NPY, KRT16, GRIK5, PI3, and RARRES1) with robustness in prediction. Low-risk patients showed favorable outcomes, high immune infiltration and high immunotherapy response. Novel ligand-receptor pairs LGALS9-HAVCR2 and CD86-CTLA4 were specifically interacted between Macro_1 and T/NK cells. VSIG4 and STAB1 were highly expressed in macrophages and were associated with poor prognosis, high tumor purity and high immune checkpoints.</p><p><strong>Conclusion: </strong>The results provide novel insights into prognosis prediction and therapeutic responses, and identify VSIG4 and STAB1 as potential biomarkers affecting macrophages in HGSOC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"159"},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}