miR Profiling Identifies XXXX Downregulation as a Potential Mechanism of Acquired @entity900 Resistance in @entity1149 .

@entity1 @entity20405 @entity137 @entity14107 @entity5 @entity1149 @entity900 @entity1442 @entity2454 @entity20406 @entity902 @entity3373
BACKGROUND: @entity1149 ( @entity1149 ) is the leading cause of @entity5 . @entity902 -based chemotherapeutic drugs are the most active agents in treating @entity1442 . Resistance to these drugs is common and multifactorial; insight into the molecular mechanisms involved will likely enhance efficacy. MATERIALS AND METHODS: A set of @entity1149 @entity902 -resistant sublines was created from the @entity1 cell line. Cell viability was quantified using the @entity2454 assay. Differentially expressed microRNAs (miRs) in these lines were identified using Affymetrix miR arrays. The potential genes targeted by these miRs were searched using the TargetScan algorithm. The expression levels of miRs and mRNA were tested using real-time polymerase chain reaction. RESULTS: @entity3373 was reproducibly elevated in all the resistant sublines tested; however, modulation of @entity3373 levels alone in these cells did not affect their response to @entity900 . A potential target of @entity3373 is @entity14107 ( @entity14107 ), an important regulator of cell proliferation. The mRNA and protein levels of @entity14107 were both downregulated in the resistant sublines. An inhibitor of @entity20405 ( @entity20406 ) protected parental @entity1149 cells from @entity900 @entity137 . CONCLUSION: In the present study, we identified miRs differentially expressed in @entity900 -resistant cell lines, including @entity3373 . A predicted target of @entity3373 is @entity14107 , and its expression was found to be downregulated in the resistant sublines, although not directly by @entity3373 . Inhibition of @entity14107 antagonizes @entity900 -induced @entity1149 cell @entity137 , suggesting that agents that inhibit @entity14107 should be avoided during @entity900 therapy.
