Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α
Abstract Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. I...
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Wiley
2018-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1527 |
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| author | Xu Chen Lei Wu Dezhi Li Yanmei Xu Luping Zhang Kai Niu Rui Kong Jiaoyang Gu Zihan Xu Zhengtang Chen Jianguo Sun |
| author_facet | Xu Chen Lei Wu Dezhi Li Yanmei Xu Luping Zhang Kai Niu Rui Kong Jiaoyang Gu Zihan Xu Zhengtang Chen Jianguo Sun |
| author_sort | Xu Chen |
| collection | DOAJ |
| description | Abstract Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR‐18a‐5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR‐18a‐5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR‐18a‐5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF‐1α) as the targets of miR‐18a‐5p. The mRNA and protein expressions of ATM and HIF‐1α were dramatically downregulated by miR‐18a‐5p in vitro and in vivo. Clinically, plasma miR‐18a‐5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR‐18a‐5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR‐18a‐5p‐high group than in miR‐18a‐5p‐low group (P < .001). A tendency demonstrated that the median local progression‐free survival (PFS) from radiotherapy was longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .281). The sensitivity and specificity of plasma miR‐18a‐5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR‐18a‐5p increases the radiosensitivity in lung cancer cells and CD133+ stem‐like cells via downregulating ATM and HIF‐1α expressions. Plasma miR‐18a‐5p would be an available indicator of radiosensitivity in lung cancer patients. |
| format | Article |
| id | doaj-art-3f8e1031232d43a2a3002a8c8ca3b8aa |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2018-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-3f8e1031232d43a2a3002a8c8ca3b8aa2024-12-20T13:15:44ZengWileyCancer Medicine2045-76342018-08-01783834384710.1002/cam4.1527Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1αXu Chen0Lei Wu1Dezhi Li2Yanmei Xu3Luping Zhang4Kai Niu5Rui Kong6Jiaoyang Gu7Zihan Xu8Zhengtang Chen9Jianguo Sun10Cancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaDepartment of Gerontology Chongqing General Hospital Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaOncology Department Leshan People’s Hospital Sichuan ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaCancer Institute, Xinqiao Hospital Army Medical University Chongqing ChinaAbstract Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR‐18a‐5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR‐18a‐5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR‐18a‐5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF‐1α) as the targets of miR‐18a‐5p. The mRNA and protein expressions of ATM and HIF‐1α were dramatically downregulated by miR‐18a‐5p in vitro and in vivo. Clinically, plasma miR‐18a‐5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR‐18a‐5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR‐18a‐5p‐high group than in miR‐18a‐5p‐low group (P < .001). A tendency demonstrated that the median local progression‐free survival (PFS) from radiotherapy was longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .281). The sensitivity and specificity of plasma miR‐18a‐5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR‐18a‐5p increases the radiosensitivity in lung cancer cells and CD133+ stem‐like cells via downregulating ATM and HIF‐1α expressions. Plasma miR‐18a‐5p would be an available indicator of radiosensitivity in lung cancer patients.https://doi.org/10.1002/cam4.1527DNA repairlung adenocarcinomamicroRNAsplasma biomarkerradiosensitivitystem‐like cells |
| spellingShingle | Xu Chen Lei Wu Dezhi Li Yanmei Xu Luping Zhang Kai Niu Rui Kong Jiaoyang Gu Zihan Xu Zhengtang Chen Jianguo Sun Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α Cancer Medicine DNA repair lung adenocarcinoma microRNAs plasma biomarker radiosensitivity stem‐like cells |
| title | Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α |
| title_full | Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α |
| title_fullStr | Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α |
| title_full_unstemmed | Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α |
| title_short | Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α |
| title_sort | radiosensitizing effects of mir 18a 5p on lung cancer stem like cells via downregulating both atm and hif 1α |
| topic | DNA repair lung adenocarcinoma microRNAs plasma biomarker radiosensitivity stem‐like cells |
| url | https://doi.org/10.1002/cam4.1527 |
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