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• W2893743543 abstract "Protein inhibitor of activated STAT 3 ( PIAS 3) is an endogenous suppressor of signal transducer and activator of transcription 3 ( STAT 3) signaling. By directly interacting with phosphorylated STAT 3, PIAS 3 can block the downstream transcriptional activity of STAT 3, which is hyper‐activated in various cancers. We previously reported that in malignant mesothelioma ( MM ), low PIAS 3 expression is associated with increased STAT 3 activation and correlates with poor patient survival, yet the regulatory mechanism(s) governing PIAS 3 expression in MM remain unclear. Here, we demonstrate that PIAS 3 protein expression does not correlate with its mRNA level in MM cell lines, indicating that PIAS 3 expression is regulated at a post‐transcriptional level. Inhibition of proteasomal degradation with MG 132 (10 μ m ) or bortezomib (1 μ m ), alone and in combination, did not increase PIAS 3 protein levels; furthermore, inhibition of protein synthesis by cycloheximide treatment did not decrease PIAS 3 levels within 48 h, suggesting that PIAS 3 expression is not actively regulated at a post‐translational level. To determine whether mi RNA (miRs) can translationally regulate PIAS 3 expression, we combined miR microarray analysis with bioinformatic screening to identify candidate miRs, in MM cell lines with low PIAS 3 expression, followed by luciferase reporter assays to validate miR regulation of the PIAS 3 3′ UTR . We identified miR‐18a as a suppressor of PIAS 3 expression that is upregulated in MM cells and whose inhibition can increase PIAS 3 expression and suppress STAT 3 activity. Moreover, we showed that miR‐18a inhibition can decrease MM cell viability and that its expression is negatively correlated with MM patient survival. Taken together, these results suggest that targeting miR‐18a may have therapeutic benefit in MM ." @default.
• W2893743543 created "2018-10-05" @default.
• W2893743543 creator A5036587861 @default.
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• W2893743543 date "2018-10-23" @default.
• W2893743543 modified "2023-09-30" @default.
• W2893743543 title "Post‐transcriptional regulation of <scp>PIAS</scp> 3 expression by miR‐18a in malignant mesothelioma" @default.
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• W2893743543 doi "https://doi.org/10.1002/1878-0261.12386" @default.
• W2893743543 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6275277" @default.
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• W2893743543 hasPublicationYear "2018" @default.
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