MicroRNAs as potential therapeutics to enhance chemosensitivity in advanced prostate cancer

Scientific Reports
Hui-Ming LinAlexander Swarbrick

Abstract

Docetaxel and cabazitaxel are taxane chemotherapy treatments for metastatic castration-resistant prostate cancer (CRPC). However, therapeutic resistance remains a major issue. MicroRNAs are short non-coding RNAs that can silence multiple genes, regulating several signalling pathways simultaneously. Therefore, synthetic microRNAs may have therapeutic potential in CRPC by regulating genes involved in taxane response and minimise compensatory mechanisms that cause taxane resistance. To identify microRNAs that can improve the efficacy of taxanes in CRPC, we performed a genome-wide screen of 1280 microRNAs in the CRPC cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment. Mimics of miR-217 and miR-181b-5p enhanced apoptosis significantly in PC3 cells in the presence of these taxanes. These mimics downregulated at least a thousand different transcripts, which were enriched for genes with cell proliferation and focal adhesion functions. Individual knockdown of a selection of 46 genes representing these transcripts resulted in toxic or taxane sensitisation effects, indicating that these genes may be mediating the effects of the microRNA mimics. A range of these genes are expressed in CRPC metastases, suggestin...Continue Reading

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Jan 3, 2019·Cytotechnology·Gizem Ors-KumogluCigir Biray-Avci
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Methods Mentioned

BETA
flow cytometry
transfection
biopsies
biopsy
xenografts
xenograft
Tandem Repeat
Assay

Software Mentioned

DIANA
FACSDiva
IncuCyte
mct
StarBase
DIANA microT
- CDS
TargetScan
Excel
MIRTarBase

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