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 doxorubicin in 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.
ABSTRACT
microRNA (miRNA) is a kind of non-coding small RNA that regulate gene expression at a post-transcriptional level by inhibiting the translation or direct degradation of specific target mRNA.Lots of studies have shown that deregulation of miRNA expression is associated with multisystem tumor.Studies on multiple myeloma (MM) have found that aberrant expression of miRNA regulate MM-cellular processes including cell proliferation,differentiation,apoptosis and drug-resistance.And they can act as diagnostic marker for MM.Some of the miRNA may even function as effective therapeutic targets.This paper reviewed the research progress of the aberrant expression of MM related miRNA in the diagnosis,pathogenesis,drug resistance of MM and its potential application as therapeutic targets.