Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Collat School of Business, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Prostate. 2023 May;83(6):590-601. doi: 10.1002/pros.24494. Epub 2023 Feb 9.
Long noncoding RNAs (lncRNAs) are RNA molecules with over 200 nucleotides that do not code for proteins, but are known to be widely expressed and have key roles in gene regulation and cellular functions. They are also found to be involved in the onset and development of various cancers, including prostate cancer (PCa). Since PCa are commonly driven by androgen regulated signaling, mainly stimulated pathways, identification and determining the influence of lncRNAs in androgen response is useful and necessary. LncRNAs regulated by the androgen receptor (AR) can serve as potential biomarkers for PCa. In the present study, gene expression data analysis were performed to distinguish lncRNAs related to the androgen response pathway.
We used publicly available RNA-sequencing and ChIP-seq data to identify lncRNAs that are associated with the androgen response pathway. Using Universal Correlation Coefficient (UCC) and Pearson Correlation Coefficient (PCC) analyses, we found 15 lncRNAs that have (a) highly correlated expression with androgen response genes in PCa and are (b) differentially expressed in the setting of treatment with an androgen agonist as well as antagonist compared to controls. Using publicly available ChIP-seq data, we investigated the role of androgen/AR axis in regulating expression of these lncRNAs. We observed AR binding in the promoter regions of 5 lncRNAs (MIR99AHG, DUBR, DRAIC, PVT1, and COLCA1), showing the direct influence of AR on their expression and highlighting their association with the androgen response pathway.
By utilizing publicly available multiomics data and by employing in silico methods, we identified five candidate lncRNAs that are involved in the androgen response pathway. These lncRNAs should be investigated as potential biomarkers for PCa.
长链非编码 RNA（lncRNA）是一种 RNA 分子，其长度超过 200 个核苷酸，不编码蛋白质，但已知广泛表达，并在基因调控和细胞功能中发挥关键作用。它们也被发现参与各种癌症的发生和发展，包括前列腺癌（PCa）。由于 PCa 通常受雄激素调节信号驱动，主要是受刺激的途径，因此鉴定和确定 lncRNA 在雄激素反应中的作用是有用且必要的。受雄激素受体（AR）调控的 lncRNA 可作为 PCa 的潜在生物标志物。在本研究中，进行了基因表达数据分析，以区分与雄激素反应途径相关的 lncRNA。
我们使用公开的 RNA-seq 和 ChIP-seq 数据来鉴定与雄激素反应途径相关的 lncRNA。使用通用相关系数（UCC）和 Pearson 相关系数（PCC）分析，我们发现了 15 个 lncRNA，它们具有（a）在 PCa 中与雄激素反应基因高度相关的表达，并且（b）在与对照相比用雄激素激动剂和拮抗剂处理时表达差异。使用公开的 ChIP-seq 数据，我们研究了雄激素/AR 轴在调节这些 lncRNA 表达中的作用。我们观察到 AR 在 5 个 lncRNA（MIR99AHG、DUBR、DRAIC、PVT1 和 COLCA1）的启动子区域结合，表明 AR 对其表达的直接影响，并强调了它们与雄激素反应途径的关联。
通过利用公开的多组学数据和采用计算方法，我们鉴定了五个参与雄激素反应途径的候选 lncRNA。这些 lncRNA 应作为 PCa 的潜在生物标志物进行研究。
