title: [Targeting miR155 restores chemotherapy sensitivity in drug-resistant myeloma cell-line RPMI8226/DOX cells].
abstract: Objective:To explore the mechanism of abnormal expression of microRNA155 (miR155) in myeloma drug-resistance to probe the possibility of inhibiting miR155 expression to restore chemotherapy sensitivity and its molecular mechanism in drug-resistant myeloma cells.Methods:Drug-resistant myeloma cell-line RPMI8226/DOX was established by culturing RPMI8226 cells with continuous low concentration and intermittent gradually increasing concentration of doxorubicinin vitro; The levels of miR155 mRNA were measured by qRT-PCR, and both proteins FOXO3a and BCL-2 expressions were detected by Western blot in cell-lines RPMI8226/S and RPMI8226/Dox. RPMI8226/DOX cells were transfected by miR155 inhibitor and mimic using gene transfer method, and then CCK-8 was used to measure proliferation and inhibition ratio, the changes of miR155 expression were detected by RT-PCR. Proteins FOXO3a and BCL-2 were detected by Western blot.Results:Comparing with RPMI8226 cells, the level of miR155 mRNA was obviously up-regulated with the relative expression of 26.860±2.340, together with increased expression of Bcl-2 protein but decreased expression of FOXO3a in RPMI8226/DOX cells. After 72 h treatment with miR155 inhibitor, the inhibition rate of transfection was 64.57%, miR155 expression decreased sharply, the level of FOXO3a expression was upregulated while BCL-2 expression decreased, chemotherapy sensitivity was restored on cell-line RPMI8226/DOX with reversed drug-resistance ratio of 2.518.Conclusions:The abnormal expression of miR155 was closely associated with myeloma drug-resistance, targeting inhibition of miR155 expression could restore chemotherapy sensitivity by increasing FOXO3a expression in drug-resistant myeloma cells.
authors.forename: C R
authors.initials: CR
authors.lastname: Xiao
authors.forename: X L
authors.initials: XL
authors.lastname: Hong
authors.forename: J S
authors.initials: JS
authors.lastname: Hu
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Haematology, Zhongshan Hospital of Xiamen University, Xiamen 361004, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D035683:MicroRNAs; D009101:Multiple Myeloma; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger
chemical_list: C000595707:BCL2 protein, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger
keywords: Drug resistance; FOXO3a; MicroRNAs; Myeloma; Neoplasm