Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types.Tumor-associated macrophages(TAMs)play a key role in promoting tumor malignant progression and therapy resistance...Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types.Tumor-associated macrophages(TAMs)play a key role in promoting tumor malignant progression and therapy resistance.However,the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic.This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo.TAMs have been found to suppress cervical cancer cells ferroptosis.Mechanistically,macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells.In cancer cells,miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis.Moreover,the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway.Importantly,in clinical cervical cancer cases,ALOX15 is negatively associated with macrophages infiltration,which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer.Moreover,both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer.Altogether,this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.展开更多
基金supported by the National Natural Science Foundation of China(81972479,U2004118,82072899,81772643 and 81772803)Natural Science Foundation of Guangdong province(2019A1515011100 and 2021A1515012576,China)+5 种基金Henan Natural Science Foundation(202300410359,China)Henan Medical Program(SBGJ2020002081,China)Guangzhou High-Level Clinical Key Specialty Construction ProjectClinical Key Specialty Construction Project of Guangzhou Medical University(202005,China)the Innovation Project of Universities in Guangdong Province(NO.2021KTSCX026,China)Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University(QNCXTD2023019,China)。
文摘Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types.Tumor-associated macrophages(TAMs)play a key role in promoting tumor malignant progression and therapy resistance.However,the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic.This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo.TAMs have been found to suppress cervical cancer cells ferroptosis.Mechanistically,macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells.In cancer cells,miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis.Moreover,the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway.Importantly,in clinical cervical cancer cases,ALOX15 is negatively associated with macrophages infiltration,which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer.Moreover,both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer.Altogether,this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.
