A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer
Abstract Objective To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. Methods Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipit...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-10874-7 |
| _version_ | 1797827530317627392 |
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| author | Chuanzhong Huang Ling Wang Huijing Chen Wankai Fu Lingdong Shao Dongmei Zhou Junxin Wu Yunbin Ye |
| author_facet | Chuanzhong Huang Ling Wang Huijing Chen Wankai Fu Lingdong Shao Dongmei Zhou Junxin Wu Yunbin Ye |
| author_sort | Chuanzhong Huang |
| collection | DOAJ |
| description | Abstract Objective To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. Methods Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. Results Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53–independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. Conclusions ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect. |
| first_indexed | 2024-04-09T12:49:48Z |
| format | Article |
| id | doaj.art-b7824a42bb774044b9e4a273b381abd3 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T12:49:48Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b7824a42bb774044b9e4a273b381abd32023-05-14T11:19:48ZengBMCBMC Cancer1471-24072023-05-0123111610.1186/s12885-023-10874-7A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancerChuanzhong Huang0Ling Wang1Huijing Chen2Wankai Fu3Lingdong Shao4Dongmei Zhou5Junxin Wu6Yunbin Ye7Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalLaboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalLaboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalDepartment of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalDepartment of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalFujian Provincial Key Laboratory of Translational Cancer MedicineFujian Provincial Key Laboratory of Translational Cancer MedicineLaboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalAbstract Objective To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. Methods Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. Results Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53–independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. Conclusions ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.https://doi.org/10.1186/s12885-023-10874-7ID3PPARγRadiotherapy efficacyPositive feedbackRectal cancer |
| spellingShingle | Chuanzhong Huang Ling Wang Huijing Chen Wankai Fu Lingdong Shao Dongmei Zhou Junxin Wu Yunbin Ye A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer BMC Cancer ID3 PPARγ Radiotherapy efficacy Positive feedback Rectal cancer |
| title | A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer |
| title_full | A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer |
| title_fullStr | A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer |
| title_full_unstemmed | A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer |
| title_short | A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer |
| title_sort | positive feedback loop between id3 and pparγ via dna damage repair regulates the efficacy of radiotherapy for rectal cancer |
| topic | ID3 PPARγ Radiotherapy efficacy Positive feedback Rectal cancer |
| url | https://doi.org/10.1186/s12885-023-10874-7 |
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