The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages...The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.展开更多
Adenomyosis is a poorly understood gynecological disorder lacking effective treatments.Controversy persists regarding“invagination”and“metaplasia”theories.The endometrial-myometrial junction(EMJ)connects the endom...Adenomyosis is a poorly understood gynecological disorder lacking effective treatments.Controversy persists regarding“invagination”and“metaplasia”theories.The endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just beginning.Using single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and EMJ.Within lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of pathogenesis.Further,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways.Cell-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT cascades.This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.展开更多
文摘The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.
基金National Natural Science Foundation of China(Nos.32270840,31721003 and 32270908)Shanghai Key Laboratory of Maternal Fetal Medicine(No.mfmkf202201)+1 种基金Natural Science Foundation of Zhejiang Province(No.LTGY24H040002)Jiaxing Municipal Public Welfare Research Project(No.2021AY30004).
文摘Adenomyosis is a poorly understood gynecological disorder lacking effective treatments.Controversy persists regarding“invagination”and“metaplasia”theories.The endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just beginning.Using single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and EMJ.Within lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of pathogenesis.Further,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways.Cell-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT cascades.This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.