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

Abstract

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.