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

Pucci, Perla; Venalainen, Erik; Alborelli, Ilaria; Quagliata, Luca; Hawkes, Cheryl; Mather, Rebecca; Romero, Ignacio A; Rigas, Sushila; Wang, Yuzhuo and Crea, Francesco (2020). LncRNA HORAS5 promotes taxane resistance in castration-resistant prostate cancer via a BCL2A1-dependent mechanism. Epigenomics, 12(13) pp. 1123–1138.

DOI: https://doi.org/10.2217/epi-2019-0316

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.

Viewing alternatives

Metrics

Item Actions

Export

You can export this page using these formats Digital Object Identifier - DOI