Li Yuwei, Xu Yunchun, Yu Xinya, Su Shuangyan, Wu Bihua, Su Yunpeng, Guo Le
Department of Medical Microbiology and Immunology, School of Basic Medical Sciences, Dali University, Dali, Yunnan, P.R. China.
Sci Rep. 2025 Feb 15;15(1):5673. doi: 10.1038/s41598-025-90416-2.
Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA, is found to be significantly dysregulated in different types of cancer, including colorectal cancer (CRC). Nevertheless, there is still much to learn about the precise functions and processes of NEAT1 in the progression of CRC. Using The Cancer Genome Atlas (TCGA) database and 50 CRC specimens from the First Affiliated Hospital of Dali University, we assessed the expression of NEAT1 to determine its clinical impact. Through gene set enrichment analysis (GSEA), Cancer Single-cell State Atlas (CancerSEA), and immune infiltration studies, we elucidated key functions of NEAT1. We utilized Cell Counting Kit-8 (CCK8), wound healing, and Transwell assays to investigate the role of NEAT1 in the progression of CRC. Through the use of GSEA and immunohistochemistry, additional investigations were conducted to unveil the downstream targets of NEAT1 and gain insights into their regulatory dynamics. Our in vitro studies confirmed the regulatory role of NEAT1 in CRC. Findings indicate that increased NEAT1 expression correlates with adverse outcomes in colorectal tissues. In the CRC model, reduced levels of NEAT1 lead to reduced cell proliferation, invasion, and migration. Additionally, NEAT1 influenced immune cell infiltration in CRC and functioned as an oncogene by upregulating Sirtuin 1 (SIRT1) expression. This study demonstrates that NEAT1 promotes CRC progression and metastasis through a SIRT1-mediated mechanism, suggesting its potential as a prognostic biomarker and therapeutic target for CRC.
核富集丰富转录本1（NEAT1）是一种长链非编码RNA，发现在包括结直肠癌（CRC）在内的不同类型癌症中显著失调。然而，关于NEAT1在CRC进展中的精确功能和过程仍有许多有待了解。利用癌症基因组图谱（TCGA）数据库和大理大学第一附属医院的50份CRC标本，我们评估了NEAT1的表达以确定其临床影响。通过基因集富集分析（GSEA）、癌症单细胞状态图谱（CancerSEA）和免疫浸润研究，我们阐明了NEAT1的关键功能。我们利用细胞计数试剂盒-8（CCK8）、伤口愈合和Transwell实验来研究NEAT1在CRC进展中的作用。通过使用GSEA和免疫组织化学，进行了额外的研究以揭示NEAT1的下游靶点并深入了解其调控动态。我们的体外研究证实了NEAT1在CRC中的调控作用。研究结果表明，NEAT1表达增加与结直肠组织的不良预后相关。在CRC模型中，NEAT1水平降低导致细胞增殖、侵袭和迁移减少。此外，NEAT1影响CRC中的免疫细胞浸润，并通过上调沉默调节蛋白1（SIRT1）的表达发挥癌基因作用。本研究表明，NEAT1通过SIRT1介导的机制促进CRC进展和转移，提示其作为CRC预后生物标志物和治疗靶点的潜力。
