Abstract：
Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.
摘要：
肺神经内分泌肿瘤（NENs）是一类以神经内分泌（NE）分化为特征的多样化肿瘤。在肺NENs中，肺类癌（LC）是一种罕见的肿瘤，具有独特的特征。最近的研究强调了转录因子（TFs）在建立肺NENs如小细胞肺癌基因表达程序中的重要性。然而,控制LC基因表达的TFs在很大程度上是未知的。在这项研究中,我们报告了称为Prospero同源盒蛋白1（PROX1）的TF在LC中的表达和潜在功能。公开可用的转录组数据表明PROX1在LC组织中高度表达，通过组织微阵列上的免疫组织化学分析证实了这一点。PROX1的敲低不影响LC衍生细胞系的细胞活力，NCI-H727。同时,转录组分析显示，PROX1敲低改变了NE分化相关基因的表达。ASCL1,CHGA,CALCA,和LINC00261被认为是PROX1的下游基因。这些发现表明，PROX1可能通过调节关键靶基因的表达在LC的NE身份中起重要作用。
