title: 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.
authors.affiliation: College of Bioengineering, Henan University of Technology, Zhengzhou, China. xujz0451@gmail.com
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Xu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liao
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Wenming
authors.initials: W
authors.lastname: Liu
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Wong
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects; D000077209:Decitabine; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology
chemical_list: D002843:Chromatin; D055504:Insulin Receptor Substrate Proteins; C556500:MIRN153 microRNA, human; D035683:MicroRNAs; D010654:Phenylbutyrates; D000077209:Decitabine; D001374:Azacitidine