食管癌的发病率在全球范围内持续增加。目前的治疗方法疗效有限，因此为了寻找更好的疾病标志物，有必要进一步阐明其分子发病机制。长非编码RNA对基因表达的调节在许多疾病中发挥作用，但在食道癌中的作用尚不清楚。本研究旨在阐明长链非编码RNA NRSN2-AS1在食管癌进展中的作用及调控机制。通过实时定量PCR、免疫组化、RNA干扰、蛋白质印迹和双荧光素酶报告基因分析，我们发现NRSN2-AS1在食管癌组织和细胞系中表达上调，且与疾病分期和预后密切相关。功能研究表明，NRSN2-AS1的沉默可抑制食管癌细胞的增殖，诱导细胞凋亡，并阻止细胞迁移和侵袭。在小鼠模型中，NRSN2-AS1 也促进肿瘤生长。转录因子 TCFL5 上调 NRSN2-AS1 的转录，后者充当 microRNA(miR)-874-5p 的海绵，从而上调癌基因 RELT 的表达。 NRSN2-AS1/miR-874-5p/RELT 调节轴的激活已在体内得到验证。版权所有 © 2024。由 Elsevier B.V. 出版。

The incidence of esophageal cancer continues to increase worldwide. Current therapeutic approaches have limited efficacy, so in order to search for better markers of the disease, it is necessary to further elucidate its molecular pathogenesis. Regulation of gene expression by long non-coding Rnas plays a role in many diseases, however the role in esophageal cancer is unclear. The aim of this study was to elucidate the role and regulatory mechanism of long non-coding RNA NRSN2-AS1 in the progression of esophageal cancer. By real-time quantitative PCR, immunohistochemistry, RNA interference, western blotting, and double luciferase reporter gene analysis, we found that NRSN2-AS1 was up-regulated in esophageal cancer tissues and cell lines, and was closely related to disease stage and prognosis. Functional studies have shown that the silencing of NRSN2-AS1 inhibits the proliferation of esophageal cancer cells, induces apoptosis, and prevents cell migration and invasion. In mouse models, NRSN2-AS1 also promoted tumor growth. The transcription factor TCFL5 upregulates the transcription of NRSN2-AS1, which acts as a sponge for microRNA(miR)-874-5p, thereby upregulating the expression of the oncogene RELT. Activation of the NRSN2-AS1/miR-874-5p/RELT regulatory axis was validated in vivo.Copyright © 2024. Published by Elsevier B.V.