Heat shock protein 90B1 plays an oncogenic role and is a target of microRNA-223 in human osteosarcoma.

摘要: Background/Aims: Over the past decade, heat shock protein 90 (Hsp90) has emerged as a potential therapeutic target for cancer. However, molecular mechanisms of down-regulation Hsp90 expression in osteosarcoma are incompletely understood. To develop therapy targeting Heat 90B1 (Hsp90B1), we studied roles miR- 223 proliferation and apoptosis human osteosarcoma. Methods: pcDNA3.1(+)- miR-223 plasmid vectors were constructed transfected into MG63 cells. Co-transfection vector with pMIR-Hsp90B1 (The recombined pMIR-GLOTM luciferase containing Hsp90B1-3′UTR) led to reduced activity dual-luciferase reporter gene assay, suggesting that Hsp90B1 is miR-223. Expression HSP90B1 was detected by RT-PCR western blotting analysis. Cell determined using MTT assay. Cell-cycle distribution examined flow cytometry. PI3K, p-Akt, Akt, mTOR, Bcl-2 Bid also After mouse xenograft model tumors constructed, tumor growth, microvessel density each group determined. Results: The pcDNA3.1(+)-miR-223 efficiently suppressed HSP90B1, while silencing increased Hsp90B1. Furthermore, overexpression results significant inhibition cell growth on culture plates. Moreover, cancer cells showed G0/G1 arrest due silencing. Protein levels PI3k, decreased, whereas increased. Microvessel assessed CD34 PCNA decreased according immunohistochemical Conclusion: direct may have suppressor function through PI3K/Akt/mTOR pathway could be used anticancer therapies