Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

中文翻译：

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Rs145204276和rs4759314通过调节GAS5 / miR-1284 / HMGB1和HOTAIR / miR-22 / HMGB1信号通路来影响前列腺癌的预后。

非编码RNA在前列腺癌（PC）的发病机理中起重要作用。这项研究旨在表征GAS5 rs145204276和HOTAIR rs4759314多态性在PC发病机理中的作用。GAS5 rs145204276的INS等位基因和HOTAIR rs4759314的A等位基因均被确定可提高PC患者的生存率。携带DEL / DEL + AG基因型的患者倾向于呈现较高水平的HMGB1，GAS5，HOTAIR和较低水平的miR-1284和miR-22。另外，rs145204276多态性的缺失等位基因增加了GAS5启动子的转录活性，而rs4759314多态性的G等位基因则增加了HOTAIR启动子的转录活性。GAS5和HOTAIR可以分别与miR-1284和miR-22结合，而miR-1284和miR-22可以与HMGB1的3'UTR结合。与对照组相比，随着GAS5或HOTAIR的存在，miR-1284或miR-22的表达降低，而HMGB1的表达在GAS5 + HOTAIR组中最高。总之，这项研究的结果表明，GAS5 rs145204276和HOTAIR rs4759314多态性均可以通过调节GAS5 / miR-1284 / HMGB1和HOTAIR / miR-22 / HMGB1信号通路来调节HMGB1的表达，从而影响PC的预后。