Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent.

BMC Cancer
Deborah A AltomareKuslima Shogen

Abstract

Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 microg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as def...Continue Reading

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Mar 13, 2014·Genomics·Max ShpakMatthew C Cowperthwaite
Apr 16, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Elena M Glinka
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Jan 14, 2021·Pharmaceutics·Jessica CastroAntoni Benito

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Datasets Mentioned

BETA
GSE17009

Methods Mentioned

BETA
Chips
Assay
PCR
ELISA
xenograft

Software Mentioned

Express ( OE
Affymetrix
Affymetrix Data 2
Onto
Cytoscape
GeneInfoVis
BioCarta
GeneChip ® Operating Software ( GCOS )

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