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长链非编码 RNA 通过 BCL2A1 依赖性机制促进去势抵抗性前列腺癌中的紫杉烷耐药性。

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

机构信息

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.

出版信息

Epigenomics. 2020 Jul;12(13):1123-1138. doi: 10.2217/epi-2019-0316. Epub 2020 Jul 3.

DOI:10.2217/epi-2019-0316
PMID:32618200
Abstract

Castration-resistant prostate cancer (CRPC) is an incurable malignancy. Long noncoding RNAs (lncRNAs) play key roles in drug resistance. LncRNA role in cabazitaxel resistance (i.e., cell-count, IC 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. expression was queried in clinical database. Cabazitaxel increased expression that upregulated , thereby protecting CRPC cells from cabazitaxel-induced apoptosis. knockdown decreased cell-count and increased apoptosis in CRPC cells. -targeting antisense oligonucleotide decreased cabazitaxel IC. In CRPC clinical samples, expression increased upon taxane treatment. stimulates the expression of BCL2A1 thereby decreasing apoptosis and enhancing cabazitaxel resistance in CRPC cells.

摘要

去势抵抗性前列腺癌(CRPC)是一种无法治愈的恶性肿瘤。长链非编码 RNA(lncRNA)在耐药性中发挥关键作用。通过慢病毒介导的过表达和基于 siRNA 的敲低研究了 lncRNA 在卡巴他赛耐药中的作用(即细胞计数、IC 和半胱天冬酶活性)。使用 RNA 测序、逆转录定量 PCR(RT-qPCR)和 Western blot 分析基因表达。在临床数据库中查询表达。卡巴他赛增加了的表达,上调了,从而保护 CRPC 细胞免受卡巴他赛诱导的细胞凋亡。敲低降低了 CRPC 细胞的细胞计数并增加了细胞凋亡。针对的反义寡核苷酸降低了卡巴他赛 IC。在 CRPC 临床样本中,在用紫杉烷治疗时表达增加。刺激 BCL2A1 的表达,从而减少细胞凋亡并增强 CRPC 细胞对卡巴他赛的耐药性。

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