Reprogramming of the microRNA transcriptome mediates resistance to rapamycin
作者： Hana Totary-Jain , Despina Sanoudou , Iddo Z. Ben-Dov , Cula N. Dautriche , Paolo Guarnieri
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摘要: The mammalian target of rapamycin (mTOR) is a central regulator cell proliferation that often deregulated in cancer. Inhibitors mTOR, including and its analogues, are being evaluated as antitumor agents. For their promise to be fulfilled, it paramount importance identify the mechanisms resistance develop novel therapies overcome it. Given emerging role microRNAs (miRNAs) tumorigenesis, we hypothesized miRNAs could play important roles response tumors mTOR inhibitors. Long-term treatment showed extensive reprogramming miRNA expression, characterized by up-regulation miR-17–92 related clusters down-regulation tumor suppressor miRNAs. Inhibition members or delivery restored sensitivity rapamycin. This study identifies new downstream components mTOR-signaling pathway, which may determine It also potential markers assess efficacy provides therapeutic targets treat rapamycin-resistant tumors.
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