Rula Sa, Xiang Zhang, Kesong Shi, Baoluri Wang, Haiquan Yu
{"title":"Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.","authors":"Rula Sa, Xiang Zhang, Kesong Shi, Baoluri Wang, Haiquan Yu","doi":"10.1186/s13048-026-02125-7","DOIUrl":"https://doi.org/10.1186/s13048-026-02125-7","url":null,"abstract":"<p><p>Natural aging affects the ovary, leading to declining function and age-related female infertility. This study investigated the role of theca-interstitial cells (TICs) in ovarian aging, a previously understudied area. Transcriptomic analysis of young and aged mouse ovaries revealed ribonucleotide reductase M2 (Rrm2)-a gene involved in DNA replication and repair-to be significantly downregulated in aged ovaries. Functional experiments revealed that Rrm2 knockdown in TICs reduced DNA synthesis, induced G1-phase arrest, inhibited proliferation, and promoted early apoptosis. Additionally, it triggered DNA damage and cellular senescence by inactivating the PI3K/AKT/mTOR pathway and upregulating p21. In vivo, RRM2 inhibition reduced primordial follicle counts, induced ovarian DNA damage, and suppressed DNA repair gene expression. Overall, these findings highlight that Rrm2 downregulation drives TIC senescence, suggesting that targeting somatic cell senescence may offer a therapeutic strategy to decelerate ovarian aging.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial intelligence in ovarian pathophysiology and management: a systematic review and meta-analysis.","authors":"Hang Yu, Lifan Peng","doi":"10.1186/s13048-026-02083-0","DOIUrl":"https://doi.org/10.1186/s13048-026-02083-0","url":null,"abstract":"<p><strong>Background: </strong>The integration of artificial intelligence (AI) into reproductive medicine and gynecologic oncology has driven transformative advances in the diagnosis, prognosis, and management of ovarian conditions, including malignancies, endocrine disorders, and functional impairments.</p><p><strong>Objective: </strong>This PRISMA 2020-compliant systematic review and meta-analysis synthesizes evidence from 81 peer-reviewed studies to evaluate the efficacy, clinical applications, and limitations of AI and machine learning (ML) models across the full spectrum of ovarian health and disease.</p><p><strong>Methods: </strong>A systematic literature search was conducted across PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Scopus for studies published between January 2015 and January 2026. Eligible studies included the development, validation, or clinical application of AI/ML models for ovarian pathophysiology or management. Study quality was appraised using the QUADAS-2 tool for diagnostic accuracy studies and the PROBAST tool for predictive modeling studies. Narrative synthesis and random-effects meta-analysis were performed, with pre-specified subgroup analyses, meta-regression, and sensitivity analyses to explore heterogeneity. Applications were categorized into ovarian cancer (diagnosis, staging, prognosis, treatment guidance), reproductive endocrinology (ovarian reserve, Polycystic Ovary Syndrome (PCOS), ovarian stimulation), and fundamental ovarian biology.</p><p><strong>Results: </strong>AI models demonstrated high diagnostic accuracy for ovarian cancer using multimodal data, including ultrasound radiomics (pooled sensitivity 89-94%, specificity 85-91%, AUC 0.92) and integrated serum biomarkers (AUC 0.94). Explainable AI (XAI) platforms effectively predicted complete surgical cytoreduction in advanced ovarian cancer (pooled AUC 0.87). In reproductive medicine, AI algorithms optimized ovarian stimulation protocols and predicted follicular growth, with reliable performance for forecasting ovarian response in IVF (pooled AUC 0.81). Substantial heterogeneity (I² 68-85% across primary analyses) was identified, driven predominantly by retrospective study design, variable AI architectures, and lack of standardized validation. Only 22% of included studies reported prospective, multicenter external validation.</p><p><strong>Conclusion: </strong>AI holds significant promise for personalizing and improving care for ovarian conditions. Translation from research to routine clinical practice requires rigorous prospective multicenter validation, standardized methodological and reporting frameworks, seamless clinical workflow integration, and robust ethical and regulatory governance to ensure responsible, equitable implementation.</p><p><strong>Trial registration: </strong>PROSPERO Registration: CRD42026348721 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42026348721.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abnormal adnexal uptake in <sup>68</sup>Ga-FAPI PET/CT: from physiological variants to malignant characterization.","authors":"Qixin Wang, Rui Sun, Canran Xiao, Xiaoliang Chen","doi":"10.1186/s13048-026-02107-9","DOIUrl":"https://doi.org/10.1186/s13048-026-02107-9","url":null,"abstract":"<p><strong>Background: </strong>The adnexal region in females presents complex imaging due to the menstrual cycle. Accurate diagnosis is crucial for effective tumor treatment. This study aims to assess the clinical utility of abnormal adnexal uptake on <sup>68</sup>Ga-FAPI PET/CT for early and precise lesion characterization.</p><p><strong>Methods: </strong>This study retrospectively analyzed all female patients with abnormal adnexal uptake on <sup>68</sup>Ga-FAPI PET/CT at our institution from November 2021 to June 2024. Semiquantitative analysis of PET/CT imaging parameters was performed, combined with serum tumor markers and immunohistochemical markers. Pathological findings or imaging follow-up ≥ 6 months served as the gold standard for evaluating the diagnostic performance of <sup>68</sup>Ga-FAPI PET/CT.</p><p><strong>Results: </strong>The study included 121 female patients with a mean age of 53.8 ± 12.2 years (18-80 years). A total of 184 adnexal lesions with abnormal uptake were identified. Pathology/follow-up confirmed 82.6% as malignancies, comprising 84 primary and 16 metastatic cases. Additionally, 2 borderline tumors and 19 benign lesions were detected. The positive predictive value was 83.5%. SUVmax differed significantly among primary malignant, metastatic, and benign lesions (12.52 ± 5.41 vs. 9.78 ± 3.39 vs. 5.52 ± 4.17). In the subset of patients with available pathological specimens, SUVmax showed weak to moderate positive correlations with Ki-67 (r = 0.361, p < 0.001) and p53 (r = 0.419, p < 0.001). Notably, the mean SUVmax in the Ki67 > 20% group was significantly higher than in the Ki67 ≤ 20% group (p < 0.001). ROC analysis showed an AUC of 0.85 of SUVmax alone for diagnosing malignant adnexal lesions, increasing to 0.89 when combined with tumor markers.</p><p><strong>Discussion: </strong><sup>68</sup>Ga-FAPI PET/CT demonstrates high diagnostic performance for ovarian lesions. Among pathologically confirmed cases, SUVmax correlates with proliferative activity and malignant potential, supporting its role in diagnostic optimization.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hecheng Zhang, Guorong Ye, Linjiao Bai, Peiyan Du, Mengjiao Wang, Furong Feng, Hongliang Li, Xueli Ma, Jiamei Lu, Jiangfeng Fan
{"title":"Vitamin E alleviates energy stress-induced injury in yak granulosa cells by blocking the AMPK/mTOR-mitophagy-ferroptosis axis.","authors":"Hecheng Zhang, Guorong Ye, Linjiao Bai, Peiyan Du, Mengjiao Wang, Furong Feng, Hongliang Li, Xueli Ma, Jiamei Lu, Jiangfeng Fan","doi":"10.1186/s13048-026-02128-4","DOIUrl":"https://doi.org/10.1186/s13048-026-02128-4","url":null,"abstract":"<p><strong>Background: </strong>Energy stress-induced dysfunction of granulosa cells (GCs) is a major etiological factor in diminished female reproductive performance. Although vitamin E affords cytoprotection to GCs, its specific mechanisms of action under energy stress conditions in the yak model remain unclear.</p><p><strong>Results: </strong>This study aimed to elucidate the pathways and cell fate decisions through which vitamin E alleviates energy stress-induced damage in yak GCs. Our results indicate that energy stress triggers a signaling cascade initiated by the AMPK-mTOR pathway, which functions as an upstream regulator for downstream events. Activation of this pathway promotes PINK1/Parkin-mediated mitophagy, leading to ferroptosis, characterized by the downregulation of SLC7A11 and GPX4 and the upregulation of ACSL4. This cascade ultimately drives the cells toward apoptosis, as evidenced by an increased Bax/Bcl-2 ratio and elevated levels of Cleaved-caspase-3, along with impaired intercellular communication due to downregulation of Cx43 and Cx37. Vitamin E intervention mitigated apoptosis and rescued the expression of gap junction proteins by intercepting this AMPK-mTOR-mitophagy-ferroptosis axis.</p><p><strong>Conclusion: </strong>Our study suggests a mechanism by which vitamin E modulates GC fate via this pathway. These findings provide insight into ovarian follicular pathophysiology in yaks and may inform strategies targeted at reproductive disorders associated with energy metabolic dysregulation.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A potential mutation-defined POLE/MMR/TP53 group classifications to stratify BRCA wild type epithelial ovarian cancer.","authors":"Yi-Ting Chen, Po-Han Lin, Yi-Jou Tai, Heng-Cheng Hsu, Kuan-Ting Kuo, Ying-Cheng Chiang","doi":"10.1186/s13048-026-02123-9","DOIUrl":"https://doi.org/10.1186/s13048-026-02123-9","url":null,"abstract":"<p><strong>Background: </strong>TCGA molecular classification has prognostic value in endometrial cancer, but its application in epithelial ovarian cancer is not clear.</p><p><strong>Methods: </strong>We investigated the somatic mutations of POLE, MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1, PMS2) and TP53, in 181 BRCA wild type EOC patients.</p><p><strong>Results: </strong>The patterns were different in histology [ serous vs. endometrioid vs. clear cell (POLEmut: 0% vs. 2.8% vs. 0%, MMRmut: 6.4% vs. 22.2% vs. 11.9%, TP53mut: 75.7% vs. 16.7% vs. 4.5%, NSMP: 17.9% vs. 58.3% vs. 83.6%, p < 0.001)]; FIGO stage [early vs. advanced (POLEmut: 1.4% vs. 0%, MMRmut: 11.3% vs. 11.8%, TP53mut: 9.8% vs. 55.5%, NSMP: 77.5% vs. 32.7%, p < 0.001)]; tumor grade [low vs. high (POLEmut: 3.8% vs. 0%, MMRmut: 19.2% vs. 10.3%, TP53mut: 11.5% vs. 41.9%, NSMP: 65.5% vs. 47.8%, p = 0.002)]; tumor recurrence [no vs. yes (POLEmut: 1.4% vs. 0%, MMRmut: 11.3% vs. 11.9%, TP53mut: 21.1% vs. 47.7%, NSMP: 66.2% vs. 40.4%, p = 0.002)] and tumor-related death [no vs. yes (POLEmut: 1.0% vs. 0%, MMRmut: 9.2% vs. 14.5%, TP53mut: 25.5% vs. 51.8%, NSMP: 64.3% vs. 33.7%, p < 0.001)]. There was difference in median disease-free survival [months (POLEmut: not reached, MMRmut: 12.5, TP53mut: 8.5, NSMP: 36.5; p = 0.002)] and overall survival [months (POLEmut: not reached, MMRmut: 41, TP53mut: 47, NSMP: not reached; p = 0.008)]. In multivariate regression analysis, R0 resection (HR: 0.54 [0.32-0.90], p < 0.001) was important prognostic factor of tumor recurrence. Platinum partial sensitive response (HR: 9.27 [3.73-23.01], p < 0.001) and platinum resistant response (HR: 26.29 [11.75-58.82], p < 0.001) were important prognostic factors of tumor-related death.</p><p><strong>Conclusions: </strong>The pattern of mutation-defined POLE/MMR/TP53 group classifications varied in histological subtypes, FIGO stage and clinical outcomes in BRCA wild type EOC. BRCA wild type EOC patients with POLEmut or NSMP had favorable survival than those with MMRmut or TP53mut. The panel could be a potential marker for EOC patients.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"YAP inactivation-mediated autophagy inhibition contributes to cisplatin resistance in ovarian cancer cells.","authors":"Ngoc Thang Nguyen, Meng-Ru Hsieh, Hieu Dac Hanh Nguyen, Waratchaya Chimphlee, Sarinporn Visitsattapongse, Wen-Tai Chiu","doi":"10.1186/s13048-026-02127-5","DOIUrl":"https://doi.org/10.1186/s13048-026-02127-5","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin resistance remains a critical barrier in the treatment of high-grade serous ovarian cancer (HGSOC). Although Hippo-YAP signaling regulates cancer progression, its contribution to cisplatin resistance is still poorly understood. Here, we demonstrate that YAP is inactivated and sequestered in the cytoplasm of cisplatin-resistant ovarian cancer cells.</p><p><strong>Results: </strong>This cytosolic retention is mediated by Hippo kinases MST1/2 and LATS1/2, as well as ERK signaling, resulting in increased phosphorylation of YAP at its inhibitory site (Ser397) and reduced phosphorylation at its activating site (Tyr357). Restoration of YAP activity through genetic overexpression or pharmacological induction of nuclear YAP accumulation significantly reversed cisplatin resistance. Mechanistically, YAP inactivation impaired cisplatin-induced autophagy. Cisplatin robustly triggered autophagy in parental cells, as evidenced by LC3 puncta formation; however, this autophagic response was blunted in resistant cells. Overexpression of YAP further suppressed LC3 puncta formation and Beclin-1 expression, and increased p62 accumulation in cisplatin-resistant ovarian cancer cells. Autophagy inhibition using 3-methyladenine (3-MA) resensitized resistant cells to cisplatin.</p><p><strong>Conclusion: </strong>Collectively, these findings reveal that YAP inactivation contributes to cisplatin resistance by abrogating autophagy formation and identify YAP reactivation as a potential strategy to overcome chemoresistance in ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiarui Zhang, Rahul Singh, Esther Man Fung Wong, Lujun Han, Grace Ho, Wan Hang Keith Chiu, Isaac Ming Kiu Cho, Philip Pun Ching Ip, Elaine Yuen Phin Lee
{"title":"Two-staged CT-based radiomics model in characterising early-stage ovarian carcinoma and benign ovarian masses.","authors":"Jiarui Zhang, Rahul Singh, Esther Man Fung Wong, Lujun Han, Grace Ho, Wan Hang Keith Chiu, Isaac Ming Kiu Cho, Philip Pun Ching Ip, Elaine Yuen Phin Lee","doi":"10.1186/s13048-026-02110-0","DOIUrl":"https://doi.org/10.1186/s13048-026-02110-0","url":null,"abstract":"<p><strong>Background: </strong>Characterisation of CT detected ovarian masses is challenging with overlapping imaging features, unreliable biomarker or clinical presentation. We proposed a two-staged CT-based radiomics model to identify early-stage ovarian carcinoma (ES-OC) and sub-classify different types of benign ovarian masses (BOM).</p><p><strong>Methods: </strong>Patients with histologically confirmed BOM or ES-OC (FIGO I-II) were retrospectively recruited from 5 centres. Radiomics features were derived from CT images using PyRadiomics (v3.0.1), which intrinsically resampled volumes to isotropic 1 mm³ voxels. To reduce feature redundancy, features with high correlation (Spearman's ρ ≥ 0.85) were excluded. Two-staged feature selection was applied. First, elastic-net regression with repeated 5-fold stratified cross-validation (100 iterations) was performed to identify highly repeatable features, followed by Mann-Whitney U testing for statistical significance. Second, Boruta algorithm with Random Forest (RF) estimator was employed over 500 iterations to robustly select features by comparing their importance to randomized shadow features. Several machine learning (ML) classifiers were evaluated using stratified 10‑fold GridSearch cross-validation with area under the curve (AUC) as tuning metric. The optimal model from each stage with highest cross-validated AUC was then evaluated on the respective test set. The AUC, calibration plot, and decision curve analysis (DCA) were employed to assess the performance and clinical utility of models.</p><p><strong>Results: </strong>The study enrolled 483 patients with 529 lesions (ES-OC: 192 patients, 192 lesions; BOM: 291 patients, 337 lesions). In the first-stage, logistic regression (LR) algorithm was selected with high sensitivity (0.870), moderate specificity (0.719) and high AUC (0.859) in the test set. In the second-stage, support vector machines (SVM) had high diagnostic accuracy with sensitivity 0.750, specificity 0.839 and AUC 0.918. DCA identified the highest benefit at 0.20 risk threshold probability in determining ES-OC.</p><p><strong>Conclusion: </strong>The two-staged CT-based radiomics model incorporating LR and SVM algorithms had high diagnostic efficiency in characterising ES-OC and BOM, potentially in triaging disease and personalising care.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"19 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816411","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}
Li Yu, Lin Wang, Baishen Pan, Beili Wang, Xi Dong, Wei Guo, Qi Che
{"title":"Identification of two novel PATL2 variants and transcriptome sequencing reveals their role in oocyte maturation.","authors":"Li Yu, Lin Wang, Baishen Pan, Beili Wang, Xi Dong, Wei Guo, Qi Che","doi":"10.1186/s13048-026-02104-y","DOIUrl":"https://doi.org/10.1186/s13048-026-02104-y","url":null,"abstract":"<p><strong>Purpose: </strong>Oocyte maturation defect (OMD) is a rare cause of female infertility characterized by the persistent arrest of oocytes at immature stages. While biallelic PATL2 variants have been associated with OMD, the underlying molecular mechanisms remain unclear. This study aimed to identify novel PATL2 variants in OMD patients and investigate their functional consequences using a Patl2 knockout (KO) mouse model.</p><p><strong>Methods: </strong>We recruited two unrelated OMD patients and performed whole-exome sequencing (WES), followed by sanger validation of candidate variants. A CRISPR/Cas9-generated Patl2 KO mouse model was established, and transcriptomic profiling of oocytes from wild-type (WT) and Patl2<sup>-/-</sup> mice was conducted to identify differentially expressed genes (DEGs) and signaling pathways.</p><p><strong>Results: </strong>We identified three PATL2 variants in the patients: a novel frameshift variant (c.99delA, p.Glu35fs), a novel synonymous variant (c.930G > A, p.K310K) confirmed by mini-gene assay to disrupt splicing and a recurrent splicing variant (c.223 - 14_223-2delCCCTCCTGTTCCA, p.R75Vfs*21). Sequence variant analysis classified these variants as pathogenic/likely pathogenic according to the ACMG/AMP guidelines. Transcriptome sequencing of Patl2<sup>-/-</sup>oocytes revealed dysregulation of key follicular development genes (Zfp36, Cited1, Fgf8, Id1, Efna1/4). KEGG pathway analysis highlighted significant upregulation of the hypoxia-inducible factor-1(HIF-1) signaling pathway and transforming growth factor-beta(TGF-beta) signaling pathway and mitogen activated protein kinase (MAPK) signaling pathway, suggesting impaired oocyte energy metabolism and disrupted granulosa-oocyte communication.</p><p><strong>Conclusion: </strong>We identified the first likely pathogenic synonymous PATL2 variant causing aberrant splicing and a novel frameshift variant in OMD, broadening the PATL2 mutational spectrum. These findings provide direct evidence for PATL2's critical role in female reproduction, where it regulates mRNA expression of proteins essential for oocyte meiotic progression and early embryonic development.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Knocking down CLDN7 enhanced the effect of cisplatin in OC cells by regulating mitophagy.","authors":"Xiushuang Zheng, Bingbing Hu, Qing Xu, Liqun Wang, Bing Han, Kexin Wang","doi":"10.1186/s13048-026-02121-x","DOIUrl":"https://doi.org/10.1186/s13048-026-02121-x","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) remains a leading cause of female mortality due to its complex pathological progression and the lack of early screening methods. The cisplatin chemotherapy resistance is a stumbling block in the treatment of ovarian cancer. Aberrant expression of Claudins (CLDNs) has been implicated in several cancers including OC, especially CLDN7, while the vital roles of CLDN7 in OC and cisplatin chemoresistance remain unclear. Methods ONCOMINE, GEPIA, the Human Protein Atlas, cBioPortal databases, CCK-8 assay, RT-PCR, Western Blot, transwell assay, Immunofluorescence (IF), rescue experiment and in vivo xenograft experiments, were utilized in this study.</p><p><strong>Results: </strong>Our research found that CLDN7 is preferentially enriched on the cytoplasmic membrane of SKOV3 cells. The expression level of CLDN7 was elevated in ovarian cancer, indicating its association with the occurrence of ovarian cancer. We discovered that CLDN7 was significantly increased in SKOV3/DDP cells, with enhanced autophagy and mitophagy levels. To further explore the possible mechanism of CLDN7 in cisplatin resistance, we knocked down CLDN7 in SKOV3/DDP cells and found that autophagy and mitophagy related proteins decreased, suggesting that CLDN7 maybe involved in cisplatin resistance by regulating autophagy and mitophagy. Colocalization of LC3 with mitochondria (MitoTracker) by immunofluorescence provides direct evidence of mitophagy. The migration and invasion ability of SKOV3/DDP cells decreased when CLDN7 was knocked down. The xenograft models experiment results indicated that silencing CLDN7 could enhance the inhibitory effect of cisplatin on tumor growth.</p><p><strong>Conclusion: </strong>Knocking down CLDN7 enhanced the effect of cisplatin in OC cells by regulating mitophagy.This provides a theoretical basis for cisplatin resistance in future studies in OC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}