RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway
Abstract Neoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-06-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2203 |
| _version_ | 1819097877710897152 |
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| author | Xueqi Yan Jie Chen You Meng Chao He Shitao Zou Peng Li Ming Chen Jinchang Wu Wei‐Qun Ding Jundong Zhou |
| author_facet | Xueqi Yan Jie Chen You Meng Chao He Shitao Zou Peng Li Ming Chen Jinchang Wu Wei‐Qun Ding Jundong Zhou |
| author_sort | Xueqi Yan |
| collection | DOAJ |
| description | Abstract Neoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of nCRT. Here, we showed that RAD18, an E3 ubiquitin‐linked enzyme, played a fundamental role in predicting the response of LARC patients to nCRT. According to clinical data, patients with low RAD18 expression level in their pre‐nCRT biopsies had a superior response to nCRT compared to those with high RAD18 expression. Inhibition of RAD18 expression in rectal cancer cells pronouncedly attenuated the proliferation and promoted apoptosis after exposing to irradiation or/and 5‐fluorouracil (5‐Fu). Downregulated RAD18 levels increased cell apoptosis by activating caspase‐9‐caspase‐3‐mediated apoptotic pathway, thus resulting in the enhancement of cell radiosensitivity and 5‐Fu susceptibility. Furthermore, a xenograft nude mouse model showed that silencing RAD18 significantly slowed tumor growth after irradiation or/and 5‐Fu in vivo. Collectively, these results implied that RAD18 could be a new biomarker to predict LARC patients who might benefit from nCRT and provide new strategies for clinical treatment of LARC. |
| first_indexed | 2024-12-22T00:22:04Z |
| format | Article |
| id | doaj.art-7397f6c0cc514b248b034b655137e24a |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-22T00:22:04Z |
| publishDate | 2019-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-7397f6c0cc514b248b034b655137e24a2022-12-21T18:45:08ZengWileyCancer Medicine2045-76342019-06-01863094310410.1002/cam4.2203RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathwayXueqi Yan0Jie Chen1You Meng2Chao He3Shitao Zou4Peng Li5Ming Chen6Jinchang Wu7Wei‐Qun Ding8Jundong Zhou9Suzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaDepartment of Oncology The Jiangyin Clinical College of Xuzhou Medical University Wuxi Jiangsu P.R. ChinaDepartment of Surgical Oncology Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaSuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaSuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaSuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaSuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaSuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaDepartment of Pathology University of Oklahoma Health Science Center Oklahoma City Oklahoma USASuzhou Cancer Center Core Laboratory Nanjing Medical University Affiliated Suzhou Hospital Suzhou Jiangsu PR ChinaAbstract Neoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of nCRT. Here, we showed that RAD18, an E3 ubiquitin‐linked enzyme, played a fundamental role in predicting the response of LARC patients to nCRT. According to clinical data, patients with low RAD18 expression level in their pre‐nCRT biopsies had a superior response to nCRT compared to those with high RAD18 expression. Inhibition of RAD18 expression in rectal cancer cells pronouncedly attenuated the proliferation and promoted apoptosis after exposing to irradiation or/and 5‐fluorouracil (5‐Fu). Downregulated RAD18 levels increased cell apoptosis by activating caspase‐9‐caspase‐3‐mediated apoptotic pathway, thus resulting in the enhancement of cell radiosensitivity and 5‐Fu susceptibility. Furthermore, a xenograft nude mouse model showed that silencing RAD18 significantly slowed tumor growth after irradiation or/and 5‐Fu in vivo. Collectively, these results implied that RAD18 could be a new biomarker to predict LARC patients who might benefit from nCRT and provide new strategies for clinical treatment of LARC.https://doi.org/10.1002/cam4.2203apoptosislocally advanced rectal cancerneoadjuvant chemoradiotherapyRAD18 |
| spellingShingle | Xueqi Yan Jie Chen You Meng Chao He Shitao Zou Peng Li Ming Chen Jinchang Wu Wei‐Qun Ding Jundong Zhou RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway Cancer Medicine apoptosis locally advanced rectal cancer neoadjuvant chemoradiotherapy RAD18 |
| title | RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway |
| title_full | RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway |
| title_fullStr | RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway |
| title_full_unstemmed | RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway |
| title_short | RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase‐9‐caspase‐3‐dependent apoptotic pathway |
| title_sort | rad18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase 9 caspase 3 dependent apoptotic pathway |
| topic | apoptosis locally advanced rectal cancer neoadjuvant chemoradiotherapy RAD18 |
| url | https://doi.org/10.1002/cam4.2203 |
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