The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma

• Published in: Cellular physiology and biochemistry Vol. 36; no. 5; pp. 2051 - 2062
• Main Authors: Shao, Xue-jun, Miao, Mei-hua, Xue, Jun, Xue, Jian, Ji, Xue-qiang, Zhu, Hong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2015
• Subjects: Antineoplastic Agents - toxicity; Bone Neoplasms - enzymology; Bone Neoplasms - pathology; Cell Division - drug effects; Cell Division - genetics; Cell Line, Tumor; Cisplatin; Cisplatin - toxicity; Down-Regulation; Humans; microRNA-497; MicroRNAs - genetics; Original Paper; Osteosarcoma; Osteosarcoma - enzymology; Osteosarcoma - pathology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; VEGFA; microRNA-497; Osteosarcoma; Cisplatin; VEGFA
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000430172

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.