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

Autor: Pucci P; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.; Present address: Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, CB20QQ, UK., Venalainen E; Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada., Alborelli I; Institute of Pathology, University Hospital Basel, Basel 4031, Switzerland., Quagliata L; Global Head of Medical Affairs, Clinical NGS & Oncology Division, Life Sciences Solutions, Thermo Fisher Scientific, Baarerstrasse, Switzerland., Hawkes C; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK., Mather R; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK., Romero I; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK., Rigas SH; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK., Wang Y; Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC V6H 3Z6, Canada.; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada., Crea F; School of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes, Buckinghamshire, MK7 6AA, UK.; Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Jazyk: angličtina
Zdroj: Epigenomics [Epigenomics] 2020 Jul; Vol. 12 (13), pp. 1123-1138. Date of Electronic Publication: 2020 Jul 03.
DOI: 10.2217/epi-2019-0316
Abstrakt: 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, IC 50 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 IC 50 . 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.
Databáze: MEDLINE