Target identification and drug discovery by data-driven hypothesis and experimental validation in ovarian endometriosis

ObjectiveTo identify targets and discover drugs for ovarian endometriosis (OE)DesignA basic study based on a data-driven hypothesis experimental validationSettingCenter Reproductive MedicinePatient(s)/Animal(s)Fourteen patients with OE 7 healthy donors were recruited, 15 female C57/BL6 mice involved.Intervention(s)Samples of lesions normal endometrium obtained. The ITPR1-knockdowned ectopic human endometrial stromal cells (HESCs) subjected to ribonucleic acid (RNA) sequencing, cell-counting kit-8 (CCK-8) assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry. Camptothecin was administered HESCs in an mouse model.Main Outcome Measure(s)ITPR1 expression endometrium, cell proliferation apoptosis ITPR1 knockdown or camptothecin treatment, autograft volume the modelResult(s)Two significant OE-relevant gene modules identified involved PI3K/Akt aging-relevant pathways. Fifteen hub genes confirmed, among which most gene, ITPR1, robustly elevated lesions. RNA sequencing revealed that highly relevant apoptosis, further confirmed by CCK-8 EdU cytometry analysis. inhibited induced HESC apoptosis. candidate targeting these screened, irinotecan as promising drugs. Both compounds suppressed apoptosis; camptothecin. therapeutic effect also validated model.Conclusion(s)This shed light use treatment. To (OE) A validation Center Medicine Fourteen involved. Samples model. model Two This