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Title: Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs [SPR1108]      
dateReleased:
08-01-2016
description:
Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCĪ± activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance. PC9 stable cell lines expressing GFP vector or miR-371-3p were generated to study the effect of miR-371-3p in response to erlotinib treatment for RNA extraction and hybridization on Affymetrix microarrays. Stable cell lines were treated with DMSO or erlotinib for 24hrs and RNA isolated for analyzing the effect of miR-371-3p on gene expression upon erlotinib treatment.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-83120
refinement:
raw
alternateIdentifiers:
83120
keywords:
functional genomics
dateModified:
08-06-2016
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AFFY-44
name:
Affymetrix GeneChip Human Genome U133 Plus 2.0 [HG-U133_Plus_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-83120/E-GEOD-83120.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-83120/E-GEOD-83120.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83120
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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