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CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma

BACKGROUND: The function of Chromobox 4 (CBX4) function has attracted attention in many cancer types due to its unique biological role; however, its mechanism in esophageal squamous cell carcinoma (ESCC) under radiotherapeutic treatment has not yet been investigated. METHODS: Silencing of CBX4 was c...

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Autores principales: Zhu, Hongcheng, Chen, Hui, Chen, Guangzong, Liu, Ming, Chu, Li, Gu, Yu, Chen, Yun, Zhang, Chi, Qin, Qin, Chen, Yanan, Chen, Weiwei, Fan, Jianhong, Nie, Yongzhan, Chen, Junqiang, Wu, Shixiu, Sun, Xinchen, Zhao, Weixin, Zhao, Kuaile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577798/
https://www.ncbi.nlm.nih.gov/pubmed/36267739
http://dx.doi.org/10.21037/atm-21-3630
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author Zhu, Hongcheng
Chen, Hui
Chen, Guangzong
Liu, Ming
Chu, Li
Gu, Yu
Chen, Yun
Zhang, Chi
Qin, Qin
Chen, Yanan
Chen, Weiwei
Fan, Jianhong
Nie, Yongzhan
Chen, Junqiang
Wu, Shixiu
Sun, Xinchen
Zhao, Weixin
Zhao, Kuaile
author_facet Zhu, Hongcheng
Chen, Hui
Chen, Guangzong
Liu, Ming
Chu, Li
Gu, Yu
Chen, Yun
Zhang, Chi
Qin, Qin
Chen, Yanan
Chen, Weiwei
Fan, Jianhong
Nie, Yongzhan
Chen, Junqiang
Wu, Shixiu
Sun, Xinchen
Zhao, Weixin
Zhao, Kuaile
author_sort Zhu, Hongcheng
collection PubMed
description BACKGROUND: The function of Chromobox 4 (CBX4) function has attracted attention in many cancer types due to its unique biological role; however, its mechanism in esophageal squamous cell carcinoma (ESCC) under radiotherapeutic treatment has not yet been investigated. METHODS: Silencing of CBX4 was carried out in TE-13 and KYSE-150 cell lines. Cell proliferation, radiosensitivity, DNA damage, apoptosis, and cell cycle distribution were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, immunofluorescence, flow cytometry, and immunoblot in vitro. In vivo xenograft models were also used to assess tumor cell growth and radioresistance. The underpinning mechanisms were explored based on pathway analysis and confirmed by rescue experiments, detecting cellular autophagy. RESULTS: Knockdown of CBX4 resulted in reduced tumor growth and enhanced radio-response in vivo and in vitro. Down-regulating CBX4 increased DNA damage, apoptotic rate, and G2/M arrest induced by radiation in ESCC cell lines. Gene Set Enrichment Analysis (GSEA) revealed that CBX4 was associated with cellular autophagy regulation. Enhanced radiosensitivity in ESCC cells silenced for CBX4 was partially blocked by autophagy inhibition (P<0.05). Beclin 1 was upregulated at the gene and protein levels in ESCC cells with CBX4 knockdown after irradiation, and overexpressing Beclin 1 reversed the radiosensitivity of ESCC cells with CBX4 knockdown (P<0.05). CONCLUSIONS: By regulating autophagic activity, CBX4 contributes to radioresistance. Targeting CBX4 might constitute an efficient approach for increasing radiosensitivity in ESCC.
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spelling pubmed-95777982022-10-19 CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma Zhu, Hongcheng Chen, Hui Chen, Guangzong Liu, Ming Chu, Li Gu, Yu Chen, Yun Zhang, Chi Qin, Qin Chen, Yanan Chen, Weiwei Fan, Jianhong Nie, Yongzhan Chen, Junqiang Wu, Shixiu Sun, Xinchen Zhao, Weixin Zhao, Kuaile Ann Transl Med Original Article BACKGROUND: The function of Chromobox 4 (CBX4) function has attracted attention in many cancer types due to its unique biological role; however, its mechanism in esophageal squamous cell carcinoma (ESCC) under radiotherapeutic treatment has not yet been investigated. METHODS: Silencing of CBX4 was carried out in TE-13 and KYSE-150 cell lines. Cell proliferation, radiosensitivity, DNA damage, apoptosis, and cell cycle distribution were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, immunofluorescence, flow cytometry, and immunoblot in vitro. In vivo xenograft models were also used to assess tumor cell growth and radioresistance. The underpinning mechanisms were explored based on pathway analysis and confirmed by rescue experiments, detecting cellular autophagy. RESULTS: Knockdown of CBX4 resulted in reduced tumor growth and enhanced radio-response in vivo and in vitro. Down-regulating CBX4 increased DNA damage, apoptotic rate, and G2/M arrest induced by radiation in ESCC cell lines. Gene Set Enrichment Analysis (GSEA) revealed that CBX4 was associated with cellular autophagy regulation. Enhanced radiosensitivity in ESCC cells silenced for CBX4 was partially blocked by autophagy inhibition (P<0.05). Beclin 1 was upregulated at the gene and protein levels in ESCC cells with CBX4 knockdown after irradiation, and overexpressing Beclin 1 reversed the radiosensitivity of ESCC cells with CBX4 knockdown (P<0.05). CONCLUSIONS: By regulating autophagic activity, CBX4 contributes to radioresistance. Targeting CBX4 might constitute an efficient approach for increasing radiosensitivity in ESCC. AME Publishing Company 2022-09 /pmc/articles/PMC9577798/ /pubmed/36267739 http://dx.doi.org/10.21037/atm-21-3630 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhu, Hongcheng
Chen, Hui
Chen, Guangzong
Liu, Ming
Chu, Li
Gu, Yu
Chen, Yun
Zhang, Chi
Qin, Qin
Chen, Yanan
Chen, Weiwei
Fan, Jianhong
Nie, Yongzhan
Chen, Junqiang
Wu, Shixiu
Sun, Xinchen
Zhao, Weixin
Zhao, Kuaile
CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title_full CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title_fullStr CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title_full_unstemmed CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title_short CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
title_sort cbx4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577798/
https://www.ncbi.nlm.nih.gov/pubmed/36267739
http://dx.doi.org/10.21037/atm-21-3630
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