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STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma

Radioresistance is the major reason for the failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates in various biological processes of malignant tumors. However, researches on its effect on radioresistance in cancers...

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Autores principales: Jiang, Kan, Yin, Xin, Zhang, Qingyi, Yin, Jie, Tang, Qiuying, Xu, Mengyou, Wu, Lingyun, Shen, Yifan, Zhou, Ziyang, Yu, Hao, Yan, Senxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929488/
https://www.ncbi.nlm.nih.gov/pubmed/36764215
http://dx.doi.org/10.1016/j.redox.2023.102626
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author Jiang, Kan
Yin, Xin
Zhang, Qingyi
Yin, Jie
Tang, Qiuying
Xu, Mengyou
Wu, Lingyun
Shen, Yifan
Zhou, Ziyang
Yu, Hao
Yan, Senxiang
author_facet Jiang, Kan
Yin, Xin
Zhang, Qingyi
Yin, Jie
Tang, Qiuying
Xu, Mengyou
Wu, Lingyun
Shen, Yifan
Zhou, Ziyang
Yu, Hao
Yan, Senxiang
author_sort Jiang, Kan
collection PubMed
description Radioresistance is the major reason for the failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates in various biological processes of malignant tumors. However, researches on its effect on radioresistance in cancers are limited. In this study, STC2 was screened out by RNA-sequencing and bioinformatics analyses as a potential prognosis predictor of ESCC radiosensitivity and then was determined to facilitate radioresistance. We found that STC2 expression is increased in ESCC tissues compared to adjacent normal tissues, and a higher level of STC2 is associated with poor prognosis. Also, STC2 mRNA and protein expression levels were higher in radioresistant cells than in their parental cells. Further investigation revealed that STC2 could interact with protein methyltransferase 5 (PRMT5) and activate PRMT5, thus leading to the increased expression of symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s). Mechanistically, STC2 can promote DDR through the homologous recombination and non-homologous end joining pathways by activating PRMT5. Meanwhile, STC2 can participate in SLC7A11-mediated ferroptosis in a PRMT5-dependent manner. Finally, these results were validated through in vivo experiments. These findings uncovered that STC2 might be an attractive therapeutic target to overcome ESCC radioresistance.
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spelling pubmed-99294882023-02-16 STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma Jiang, Kan Yin, Xin Zhang, Qingyi Yin, Jie Tang, Qiuying Xu, Mengyou Wu, Lingyun Shen, Yifan Zhou, Ziyang Yu, Hao Yan, Senxiang Redox Biol Research Paper Radioresistance is the major reason for the failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates in various biological processes of malignant tumors. However, researches on its effect on radioresistance in cancers are limited. In this study, STC2 was screened out by RNA-sequencing and bioinformatics analyses as a potential prognosis predictor of ESCC radiosensitivity and then was determined to facilitate radioresistance. We found that STC2 expression is increased in ESCC tissues compared to adjacent normal tissues, and a higher level of STC2 is associated with poor prognosis. Also, STC2 mRNA and protein expression levels were higher in radioresistant cells than in their parental cells. Further investigation revealed that STC2 could interact with protein methyltransferase 5 (PRMT5) and activate PRMT5, thus leading to the increased expression of symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s). Mechanistically, STC2 can promote DDR through the homologous recombination and non-homologous end joining pathways by activating PRMT5. Meanwhile, STC2 can participate in SLC7A11-mediated ferroptosis in a PRMT5-dependent manner. Finally, these results were validated through in vivo experiments. These findings uncovered that STC2 might be an attractive therapeutic target to overcome ESCC radioresistance. Elsevier 2023-02-03 /pmc/articles/PMC9929488/ /pubmed/36764215 http://dx.doi.org/10.1016/j.redox.2023.102626 Text en © 2023 The Authors 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 Research Paper
Jiang, Kan
Yin, Xin
Zhang, Qingyi
Yin, Jie
Tang, Qiuying
Xu, Mengyou
Wu, Lingyun
Shen, Yifan
Zhou, Ziyang
Yu, Hao
Yan, Senxiang
STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title_full STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title_fullStr STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title_full_unstemmed STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title_short STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
title_sort stc2 activates prmt5 to induce radioresistance through dna damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929488/
https://www.ncbi.nlm.nih.gov/pubmed/36764215
http://dx.doi.org/10.1016/j.redox.2023.102626
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