The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma
Background: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/430172 |
| _version_ | 1818309835275370496 |
|---|---|
| author | Xue-jun Shao Mei-hua Miao Jun Xue Jian Xue Xue-qiang Ji Hong Zhu |
| author_facet | Xue-jun Shao Mei-hua Miao Jun Xue Jian Xue Xue-qiang Ji Hong Zhu |
| author_sort | Xue-jun Shao |
| collection | DOAJ |
| description | Background: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. Methods: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. Results: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. Conclusion: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells. |
| first_indexed | 2024-12-13T07:36:29Z |
| format | Article |
| id | doaj.art-70e5d4cb132442279172c730b1083ca9 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T07:36:29Z |
| publishDate | 2015-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-70e5d4cb132442279172c730b1083ca92022-12-21T23:55:05ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013652051206210.1159/000430172430172The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in OsteosarcomaXue-jun ShaoMei-hua MiaoJun XueJian XueXue-qiang JiHong ZhuBackground: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. Methods: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. Results: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. Conclusion: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.http://www.karger.com/Article/FullText/430172VEGFACisplatinOsteosarcomamicroRNA-497 |
| spellingShingle | Xue-jun Shao Mei-hua Miao Jun Xue Jian Xue Xue-qiang Ji Hong Zhu The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma Cellular Physiology and Biochemistry VEGFA Cisplatin Osteosarcoma microRNA-497 |
| title | The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma |
| title_full | The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma |
| title_fullStr | The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma |
| title_full_unstemmed | The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma |
| title_short | The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma |
| title_sort | down regulation of microrna 497 contributes to cell growth and cisplatin resistance through pi3k akt pathway in osteosarcoma |
| topic | VEGFA Cisplatin Osteosarcoma microRNA-497 |
| url | http://www.karger.com/Article/FullText/430172 |
| work_keys_str_mv | AT xuejunshao thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT meihuamiao thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT junxue thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT jianxue thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT xueqiangji thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT hongzhu thedownregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT xuejunshao downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT meihuamiao downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT junxue downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT jianxue downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT xueqiangji downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma AT hongzhu downregulationofmicrorna497contributestocellgrowthandcisplatinresistancethroughpi3kaktpathwayinosteosarcoma |