LncRNA HORAS5 promotes taxane resistance in castration-resistant prostate cancer via a BCL2A1-dependent mechanism.
Perla PucciErik VenalainenIlaria AlborelliLuca QuagliataCheryl HawkesRebecca L MatherIgnacio RomeroSushilaben H RigasYuzhuo WangFrancesco CreaPublished in: Epigenomics (2020)
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.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- poor prognosis
- oxidative stress
- cell cycle arrest
- signaling pathway
- cell death
- long non coding rna
- single cell
- binding protein
- stem cells
- cell therapy
- emergency department
- genome wide
- mesenchymal stem cells
- high resolution
- drug delivery
- replacement therapy
- pi k akt
- network analysis