Department of Urology, Shanghai 9Th People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.
BMC Med Genomics. 2021 Dec 11;14(1):291. doi: 10.1186/s12920-021-01135-2.
Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease.
High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro.
Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes.
These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.
派杰氏病（EMPD）是一种罕见的恶性表皮内腺癌，其发病机制尚不清楚。调节性长链非编码 RNA（lncRNA）在许多物种中都有特征，并且参与了发育和病理学等过程，在不同的疾病中揭示了新的调控层，尤其是在癌症研究中。在本研究中，我们使用高通量测序技术揭示了派杰氏病中的 lncRNA-mRNA 相互作用网络。
使用高通量测序技术鉴定 EMPD 患者和健康对照之间差异表达的 lncRNA 和 mRNA 谱。然后，进行了一系列生物信息学分析，构建了 lncRNA-mRNA 相互作用网络，并最终在体外进行了验证。
共收集了 6 对 EMPD 肿瘤和正常皮肤样本进行测序，以鉴定 EMPD 与健康对照组之间差异表达的 lncRNA 和 mRNA 谱。共鉴定出 997 个差异表达的 mRNA 和 785 个差异表达的 lncRNA。GO 和 KEGG 分析表明，表皮发育和细胞黏附在 EMPD 中起重要作用。lncRNA-mRNA 相互作用网络分析的结果表明，NEAT1、PGAP1、FKBP5 和 CDON 是网络的关键节点，lncRNA NEAT1 可能调节 mRNA PGAP1、FKBP5 和 CDON。在另外 10 名患者中进行的实时定量 RT-PCR 分析结果与测序分析结果一致。此外，在人永生化角质形成细胞中进行的体外实验证实了 NEAT1 与 PGAP1、FKBP5 和 CDON 之间的相互作用。
这些发现表明，基于 4 个关键节点（NEAT1、PGAP1、FKBP5 和 CDON）的 lncRNA-mRNA 相互作用网络可能在 EMPD 中发挥重要作用，这将有助于深入了解 EMPD 的发病机制。
