title: Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies.
abstract: Glucocorticoid (GC) resistance in lymphoblastic malignancies is related to treatment failure and is a marker of poor prognosis. Previous studies have suggested that microRNA-182 (miR-182) functions as an oncogene and plays a role in tumorigenesis, through regulation of FOXO3A. FOXO3A has been implicated in tumor suppression and GC-induced apoptosis, suggesting that FOXO3A has potential as a therapeutic target. Herein we investigated the role of miR-182 in GC sensitivity in lymphoblastic malignancies. Expression of miR-182 was consistently higher in human and mouse GC-resistant cell lines than in GC-sensitive cell lines. Furthermore, increased expression of miR-182 reduced total FOXO3A expression but had no significant effect on phospho-FOXO3A. Additionally Bim, as a downstream target of FOXO3A, was reduced by overexpression of miR-182, and increased by down-regulation of miR-182. These results demonstrate that miR-182 is involved in glucocorticoid resistance, via targeting of FOXO3A, and that restoration of miR-182 is a potentially promising therapeutic strategy in lymphoblastic malignancies.
authors.affiliation: The Hematology Department of Huadong Hospital Affiliated to Fudan University, Shanghai, China.
authors.forename: Apeng
authors.initials: A
authors.lastname: Yang
authors.forename: Jiexian
authors.initials: J
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Wenming
authors.initials: W
authors.lastname: Qin
authors.forename: Botao
authors.initials: B
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Youxin
authors.initials: Y
authors.lastname: Jin
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D008565:Membrane Proteins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D011518:Proto-Oncogene Proteins; D003907:Dexamethasone