MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1
Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-02-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/460505 |
| _version_ | 1811198378508288000 |
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| author | Peng Li Xiao Yang Yidong Cheng Xiaolei Zhang Chengdi Yang Xiaheng Deng Pengchao Li Jun Tao Haiwei Yang Jifu Wei Jingyuan Tang Wenbo Yuan Qiang Lu Xiaoting Xu Min Gu |
| author_facet | Peng Li Xiao Yang Yidong Cheng Xiaolei Zhang Chengdi Yang Xiaheng Deng Pengchao Li Jun Tao Haiwei Yang Jifu Wei Jingyuan Tang Wenbo Yuan Qiang Lu Xiaoting Xu Min Gu |
| author_sort | Peng Li |
| collection | DOAJ |
| description | Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer. |
| first_indexed | 2024-04-12T01:29:56Z |
| format | Article |
| id | doaj.art-a99ebd9f07904a09a4ddcf6339d12b47 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T01:29:56Z |
| publishDate | 2017-02-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-a99ebd9f07904a09a4ddcf6339d12b472022-12-22T03:53:31ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-02-0141392193210.1159/000460505460505MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1Peng LiXiao YangYidong ChengXiaolei ZhangChengdi YangXiaheng DengPengchao LiJun TaoHaiwei YangJifu WeiJingyuan TangWenbo YuanQiang LuXiaoting XuMin GuBackground/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.http://www.karger.com/Article/FullText/460505MiR-218Glut1CisplatinChemo-sensitivityBladder cancer |
| spellingShingle | Peng Li Xiao Yang Yidong Cheng Xiaolei Zhang Chengdi Yang Xiaheng Deng Pengchao Li Jun Tao Haiwei Yang Jifu Wei Jingyuan Tang Wenbo Yuan Qiang Lu Xiaoting Xu Min Gu MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 Cellular Physiology and Biochemistry MiR-218 Glut1 Cisplatin Chemo-sensitivity Bladder cancer |
| title | MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 |
| title_full | MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 |
| title_fullStr | MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 |
| title_full_unstemmed | MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 |
| title_short | MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1 |
| title_sort | microrna 218 increases the sensitivity of bladder cancer to cisplatin by targeting glut1 |
| topic | MiR-218 Glut1 Cisplatin Chemo-sensitivity Bladder cancer |
| url | http://www.karger.com/Article/FullText/460505 |
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