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      Chromatin-modifying drugs induce miRNA-153 expression to suppress Irs-2 in glioblastoma cell lines.

      International Journal of Cancer. Journal International du Cancer
      Azacitidine, analogs & derivatives, pharmacology, Cell Line, Tumor, Chromatin, drug effects, Glioblastoma, genetics, Humans, Insulin Receptor Substrate Proteins, metabolism, MicroRNAs, Phenylbutyrates

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          MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression by inhibiting translation or by promoting mRNA degradation. Previously, we established that microRNA-153 (miR-153) induces apoptosis by downregulating B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1) protein expression levels in glioblastoma cell line DBTRG-05MG. In our study, we show that ectopic expression of miR-153 also inhibits the protein kinase B (PKB/Akt) pathway via reducing the protein level of insulin receptor substrate-2 (Irs-2). Moreover, simultaneous treatment with the chromatin-modifying drugs 4-phenylbutyric acid and 5-aza-2'-deoxycytidine induces miR-153 expression to suppress Irs-2, Bcl-2 and Mcl-1 expressions, thus downregulating the survival but upregulating the apoptotic pathways, implying that tumor suppressor miR-153 is a dual life and death regulator. Copyright © 2011 UICC.

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