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The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

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 s...

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Autores principales: Luo, Yanlin, Chen, Yibing, Jin, Huan, Hou, Benxin, Li, Hongsheng, Li, Xiang, Liu, Lingfeng, Zhou, Yuan, Li, Yonghua, Song, Yong Sang, Liu, Quentin, Zou, Zhengzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326300/
https://www.ncbi.nlm.nih.gov/pubmed/37425043
http://dx.doi.org/10.1016/j.apsb.2023.03.025
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author Luo, Yanlin
Chen, Yibing
Jin, Huan
Hou, Benxin
Li, Hongsheng
Li, Xiang
Liu, Lingfeng
Zhou, Yuan
Li, Yonghua
Song, Yong Sang
Liu, Quentin
Zou, Zhengzhi
author_facet Luo, Yanlin
Chen, Yibing
Jin, Huan
Hou, Benxin
Li, Hongsheng
Li, Xiang
Liu, Lingfeng
Zhou, Yuan
Li, Yonghua
Song, Yong Sang
Liu, Quentin
Zou, Zhengzhi
author_sort Luo, Yanlin
collection PubMed
description 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.
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spelling pubmed-103263002023-07-08 The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes Luo, Yanlin Chen, Yibing Jin, Huan Hou, Benxin Li, Hongsheng Li, Xiang Liu, Lingfeng Zhou, Yuan Li, Yonghua Song, Yong Sang Liu, Quentin Zou, Zhengzhi Acta Pharm Sin B Original Article 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. Elsevier 2023-06 2023-03-31 /pmc/articles/PMC10326300/ /pubmed/37425043 http://dx.doi.org/10.1016/j.apsb.2023.03.025 Text en © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Luo, Yanlin
Chen, Yibing
Jin, Huan
Hou, Benxin
Li, Hongsheng
Li, Xiang
Liu, Lingfeng
Zhou, Yuan
Li, Yonghua
Song, Yong Sang
Liu, Quentin
Zou, Zhengzhi
The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title_full The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title_fullStr The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title_full_unstemmed The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title_short The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
title_sort suppression of cervical cancer ferroptosis by macrophages: the attenuation of alox15 in cancer cells by macrophages-derived exosomes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326300/
https://www.ncbi.nlm.nih.gov/pubmed/37425043
http://dx.doi.org/10.1016/j.apsb.2023.03.025
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