Chen Y.Tsai Y.-H.Tseng B.-J.Pan H.-Y.SHENG-HONG TSENG2020-03-122020-03-1220160022-3468https://www.scopus.com/inward/record.uri?eid=2-s2.0-84991380297&doi=10.1016%2fj.jpedsurg.2016.07.003&partnerID=40&md5=21702b2c239449b8bf3130a63fb866ebhttps://scholars.lib.ntu.edu.tw/handle/123456789/476129Background Mammalian target of rapamycin (mTOR) inhibitors exert significant antitumor effects on several cancer cell types. In this study, we investigated the effects of mTOR inhibitors, in particular the regulation of the microRNA, in neuroblastoma cells. Methods AZD8055 (a new mTOR inhibitor)- or rapamycin-induced cytotoxic effects on neuroblastoma cells were studied. Western blotting was used to investigate the expression of various proteins in the mTOR pathway. MicroRNA precursors and antagomirs were transfected into cells to manipulate the expression of target microRNA. Results AZD8055 exerted stronger cytotoxic effects than rapamycin in neuroblastoma cells (p?<?0.03). In addition, AZD8055 suppressed the mTOR pathway and increased the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in the neuroblastoma cells. AZD8055 significantly decreased miR-19b expression (p?<?0.005); in contrast, rapamycin increased miR-19b expression (p?<?0.05). Transfection of miR-19b antagomir into the neuroblastoma cells mimicked the effects of AZD8055 treatment, whereas miR-19b overexpression reversed the effects of AZD8055. Combination of miR-19b knockdown and rapamycin treatment significantly improved the sensitivity of neuroblastoma cells to rapamycin (p?<?0.02). Conclusion Suppression of miR-19b may enhance the cytotoxic effects of mTOR inhibitors in neuroblastoma cells. ? 2016 Elsevier Inc.AZD8055; miR-19b; mTOR; Neuroblastoma[SDGs]SDG3antagomir; azd 8055; DNA nucleotidylexotransferase; microRNA; microRNA 19b; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; rapamycin; unclassified drug; (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; immunosuppressive agent; microRNA; MIRN19 microRNA, human; morpholine derivative; MTOR protein, human; rapamycin; RNA; target of rapamycin kinase; apoptosis; Article; cell viability; DNA fragmentation; drug cytotoxicity; gene overexpression; genetic transfection; human; human cell; neuroblastoma cell; priority journal; real time polymerase chain reaction; RNA extraction; signal transduction; TUNEL assay; Western blotting; antagonists and inhibitors; gene expression regulation; genetics; metabolism; neuroblastoma; pathology; tumor cell line; Blotting, Western; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Immunosuppressive Agents; MicroRNAs; Morpholines; Neuroblastoma; Real-Time Polymerase Chain Reaction; RNA, Neoplasm; Sirolimus; TOR Serine-Threonine Kinasesjournal article10.1016/j.jpedsurg.2016.07.003274928192-s2.0-84991380297