PROX1 is a regulator of neuroendocrine-related gene expression in lung carcinoid

IF 4.3 3区生物学

Human Cell Pub Date : 2024-07-27 DOI:10.1007/s13577-024-01109-3

Kouhei Sakurai, Tatsuya Ando, Yasuhiro Sakai, Yuichiro Mori, Satoru Nakamura, Taku Kato, Hiroyasu Ito

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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.

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PROX1是肺类癌中神经内分泌相关基因表达的调节因子

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。在肺神经内分泌肿瘤中，肺类癌（LC）是一种具有独特特征的罕见肿瘤。最近的研究强调了转录因子（TFs）在小细胞肺癌等肺部 NENs 中建立基因表达程序的重要性。然而，控制 LC 基因表达的转录因子在很大程度上还不为人所知。在本研究中，我们报告了一种名为 Prospero homeobox protein1 (PROX1) 的 TF 在 LC 中的表达和潜在功能。公开的转录组数据表明，PROX1 在 LC 组织中高表达，组织芯片上的免疫组化分析证实了这一点。敲除 PROX1 不会影响 LC 衍生细胞系 NCI-H727 的细胞活力。同时，转录组分析表明，PROX1 基因敲除改变了参与NE分化的基因的表达。ASCL1、CHGA、CALCA和LINC00261被认为是PROX1的下游基因。这些发现表明，PROX1可能通过调控关键靶基因的表达，在LC的NE特性中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.