Abstract：
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.
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.
摘要：
乳腺外Paget病（EMPD）是一种罕见的恶性表皮内腺癌，对其了解甚少。调节性长非编码RNA（lncRNAs）在许多物种中具有特征，并显示参与发育和病理等过程。揭示了不同疾病的新监管层，特别是在癌症研究中。在本研究中,我们使用高通量测序来揭示乳房外Paget病的lncRNA-mRNA相互作用网络。
高通量测序用于鉴定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以构建lncRNA-mRNA相互作用网络，最终在体外得到证实。
收集六对EMPD肿瘤和正常皮肤样品并测序以鉴定EMPD和健康对照之间差异表达的lncRNA和mRNA谱。鉴定了总共997个差异表达的mRNA和785个差异表达的lncRNA。GO和KEGG分析表明，表皮发育和细胞粘附在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，并且lncRNANEAT1可能调节PGAP1，FKBP5和CDON的mRNA。在其他10例患者中进行的NEAT1，PGAP1，FKBP5和CDON的定量实时RT-PCR结果与测序分析的结果一致。此外，体外实验证实了NEAT1和PGAP1，FKBP5和CDON在人永生化角质形成细胞中的相互作用。
这些发现表明，基于四个关键节点的lncRNA-mRNA相互作用网络，NEAT1、PGAP1FKBP5和CDON，可能在EMPD中发挥重要作用，这将有助于更深入地了解EMPD的发病机制。
高通量测序用于鉴定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以构建lncRNA-mRNA相互作用网络，最终在体外得到证实。
收集六对EMPD肿瘤和正常皮肤样品并测序以鉴定EMPD和健康对照之间差异表达的lncRNA和mRNA谱。鉴定了总共997个差异表达的mRNA和785个差异表达的lncRNA。GO和KEGG分析表明，表皮发育和细胞粘附在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，并且lncRNANEAT1可能调节PGAP1，FKBP5和CDON的mRNA。在其他10例患者中进行的NEAT1，PGAP1，FKBP5和CDON的定量实时RT-PCR结果与测序分析的结果一致。此外，体外实验证实了NEAT1和PGAP1，FKBP5和CDON在人永生化角质形成细胞中的相互作用。
这些发现表明，基于四个关键节点的lncRNA-mRNA相互作用网络，NEAT1、PGAP1FKBP5和CDON，可能在EMPD中发挥重要作用，这将有助于更深入地了解EMPD的发病机制。
