由于基因组研究的许多进展，我们对长非编码RNA（lncRNA）在健康和疾病状态中的功能的理解在过去几十年中有所发展。在本研究中，我们对与三阴性乳腺癌（TNBC，n = 42）和雌激素受体（ER+，n = 42）乳腺癌相比正常乳腺组织（n = 56）富集的lncRNA转录组进行了表征。鉴于TNBC的侵袭性特点，我们的数据显示在TNBC中选择性富集了57个lncRNA。其中，我们选择了AC099850.4 lncRNA进行进一步研究，在第二个TNBC队列（n = 360）中进一步证实了其表达的升高，并且其表达与较差的预后相关。AC099850.4高表达的TNBC的网络分析显示在细胞周期激活和有丝分裂等功能类别中存在富集。对AC099850.4高表达的TNBC中差异表达基因进行的Ingenuity通路分析显示其激活了经典的着丝粒中期信号通路、吡哆醛5'-磷酸盐拯救通路和嘧啶核苷酸拯救通路。此外，上游调控分析预测了几个上游调控网络的激活，包括CKAP2L、FOXM1、RABL6、PCLAF和MITF，而TP53、NUPR1、TRPS1和CDKN1A的上游调控网络被抑制。有趣的是，AC099850.4的高表达与更差的短期无复发生存率相关（log-rank p = 0.01）。综上所述，我们的数据首次揭示了AC099850.4作为TNBC中不利的预后标志物，与更具侵袭性的临床病理特征相关，并提示其作为TNBC的预后生物标志物和治疗靶点的潜在利用。版权所有 © 2023 Vishnubalaji和Alajez。

Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and estrogen receptor (ER+, n = 42) breast cancer compared to normal breast tissue (n = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC. Among those, AC099850.4 lncRNA was chosen for further investigation where it exhibited elevated expression, which was further confirmed in a second TNBC cohort (n = 360) where its expression correlated with a worse prognosis. Network analysis of AC099850.4high TNBC highlighted enrichment in functional categories indicative of cell cycle activation and mitosis. Ingenuity pathway analysis on the differentially expressed genes in AC099850.4high TNBC revealed the activation of the canonical kinetochore metaphase signaling pathway, pyridoxal 5'-phosphate salvage pathway, and salvage pathways of pyrimidine ribonucleotides. Additionally, upstream regulator analysis predicted the activation of several upstream regulator networks including CKAP2L, FOXM1, RABL6, PCLAF, and MITF, while upstream regulator networks of TP53, NUPR1, TRPS1, and CDKN1A were suppressed. Interestingly, elevated expression of AC099850.4 correlated with worse short-term relapse-free survival (log-rank p = 0.01). Taken together, our data are the first to reveal AC099850.4 as an unfavorable prognostic marker in TNBC, associated with more aggressive clinicopathological features, and suggest its potential utilization as a prognostic biomarker and therapeutic target in TNBC.Copyright © 2023 Vishnubalaji and Alajez.