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LncRNA HORAS5 promotes taxane resistance in castration-resistant prostate cancer via a BCL2A1-dependent mechanism.

Published version
Peer-reviewed

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Authors

Pucci, Perla 
Venalainen, Erik 
Alborelli, Ilaria 
Quagliata, Luca 
Hawkes, Cheryl 

Abstract

Background: Castration-resistant prostate cancer (CRPC) is an incurable malignancy. Long noncoding RNAs (lncRNAs) play key roles in drug resistance. Materials & methods: LncRNA HORAS5 role in cabazitaxel resistance (i.e., cell-count, IC50 and caspase activity) was studied via lentiviral-mediated overexpression and siRNA-based knockdown. Genes expression was analyzed with RNA-sequencing, reverse transcription quantitative PCR (RT-qPCR) and western blot. HORAS5 expression was queried in clinical database. Results: Cabazitaxel increased HORAS5 expression that upregulated BCL2A1, thereby protecting CRPC cells from cabazitaxel-induced apoptosis. BCL2A1 knockdown decreased cell-count and increased apoptosis in CRPC cells. HORAS5-targeting antisense oligonucleotide decreased cabazitaxel IC50. In CRPC clinical samples, HORAS5 expression increased upon taxane treatment. Conclusion:HORAS5 stimulates the expression of BCL2A1 thereby decreasing apoptosis and enhancing cabazitaxel resistance in CRPC cells.

Description

Keywords

BCL2A1, HORAS5, castration-resistant prostate cancer, drug resistance, lncRNA, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Cell Proliferation, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Humans, Male, Minor Histocompatibility Antigens, Oligonucleotides, Antisense, Prostatic Neoplasms, Castration-Resistant, Proto-Oncogene Proteins c-bcl-2, RNA, Long Noncoding, Taxoids

Journal Title

Epigenomics

Conference Name

Journal ISSN

1750-1911
1750-192X

Volume Title

12

Publisher

Future Medicine Ltd