通过RNA-seq分析已经鉴定出了数以万计的长非编码RNA（lncRNA），但其生物学和病理学意义仍不清楚。通过将全基因组lncRNA数据与PDAC GWAS的跨人类群Meta分析相结合，我们绘制了一个全面的胰腺导管腺癌（PDAC）相关lncRNA图谱，包括1,204个lncRNA（其中包括445个新的lncRNA和759个GENCODE注释的lncRNA）和4,368个变异体。此外，我们发现，PDAC相关lncRNA可以通过改变染色质活性、转录因子和RNA结合蛋白的结合亲和力来发挥功能。重要的是，与PDAC相关的遗传变异优先出现在PDAC相关的lncRNA区域，支持PDAC相关lncRNA的生物学和临床相关性。最后，我们将RP11-638I2.4的一个新转录本（MICT00000110172.1）优先考虑作为潜在的肿瘤促进因子。MICT00000110172.1能够增强与YY1的相互作用，可以逆转YY1对胰腺癌细胞周期停滞的效应，促进胰腺癌的生长。MICT00000110172.1第二外显子上的rs2757535的G > A变化引起了空间结构的改变，并创建了一个YY1结合的靶区，从而以等位基因特异性的方式加强了MICT00000110172.1的效应，并增加了肿瘤发生的易感性。总之，我们的结果扩展了PDAC相关lncRNA的库存，这为未来的功能探索和lncRNA靶向治疗的鉴定提供了一个起点。© 2023。作者（们），在Springer Nature下由Springer-Verlag GmbH Germany独家许可。

Tens of thousands of long non-coding RNAs (lncRNAs) have been identified through RNA-seq analysis, but the biological and pathological significance remains unclear. By integrating the genome-wide lncRNA data with a cross-ancestry meta-analysis of PDAC GWASs, we depicted a comprehensive atlas of pancreatic ductal adenocarcinoma (PDAC)-associated lncRNAs, containing 1,204 lncRNA (445 novel lncRNAs and 759 GENCODE annotated lncRNAs) and 4,368 variants. Furthermore, we found that PDAC-associated lncRNAs could function by altering chromatin activity, transcription factors, and RNA-binding proteins binding affinity. Importantly, genetic variants linked to PDAC are preferentially found at PDAC-associated lncRNA regions, supporting the biological and clinical relevance of PDAC-associated lncRNAs. Finally, we prioritized a novel transcript (MICT00000110172.1) of RP11-638I2.4 as a potential tumor promoter. MICT00000110172.1 is able to reinforce the interaction with YY1, which could reverse the effect of YY1 on pancreatic cancer cell cycle arrest to promote the pancreatic cancer growth. G > A change at rs2757535 in the second exon of MICT00000110172.1 induces a spatial structural change and creates a target region for YY1 binding, which enforces the effect of MICT00000110172.1 in an allele-specific manner, and thus confers susceptibility to tumorigenesis. In summary, our results extend the repertoire of PDAC-associated lncRNAs that could act as a starting point for future functional explorations, and the identification of lncRNA-based target therapy.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.