Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells

Abstract Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk...

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Main Authors: Yuxiang Zhang, Zhiman Zhu, Naihan Ren, Dongni Wang, Xue Zeng, Na Zhang
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-77811-x
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author Yuxiang Zhang
Zhiman Zhu
Naihan Ren
Dongni Wang
Xue Zeng
Na Zhang
author_facet Yuxiang Zhang
Zhiman Zhu
Naihan Ren
Dongni Wang
Xue Zeng
Na Zhang
author_sort Yuxiang Zhang
collection DOAJ
description Abstract Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes.
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spelling doaj-art-c891d02fce524d2b8c5c679dbca67edc2024-11-10T12:19:28ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-77811-xImplication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cellsYuxiang Zhang0Zhiman Zhu1Naihan Ren2Dongni Wang3Xue Zeng4Na Zhang5Department of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLaboratory of Clinical and Experimental Pathology, Xuzhou Medical UniversityDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteAbstract Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes.https://doi.org/10.1038/s41598-024-77811-xCCNG1Esophageal squamous cell carcinoma (ESCC)RadioresistanceWnt/β-catenin pathway
spellingShingle Yuxiang Zhang
Zhiman Zhu
Naihan Ren
Dongni Wang
Xue Zeng
Na Zhang
Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
Scientific Reports
CCNG1
Esophageal squamous cell carcinoma (ESCC)
Radioresistance
Wnt/β-catenin pathway
title Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
title_full Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
title_fullStr Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
title_full_unstemmed Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
title_short Implication of CCNG1 in radiosensitivity via the Wnt/β-catenin pathway in esophageal squamous cells
title_sort implication of ccng1 in radiosensitivity via the wnt β catenin pathway in esophageal squamous cells
topic CCNG1
Esophageal squamous cell carcinoma (ESCC)
Radioresistance
Wnt/β-catenin pathway
url https://doi.org/10.1038/s41598-024-77811-x
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