Xu Yangwei, Li Yanyan, Qiu Yue, Sun Fei, Zhu Guifang, Sun Jingbo, Cai Guixing, Lin Wanmei, Fu Yun, Wu Hongmei, Jiang Shanshan, Wen Zhihui, Feng Feiyan, Luo Junjie, Yang Yuqin, Zhang Qingling
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Department of Pathology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Cell Dev Biol. 2021 Sep 6;9:705697. doi: 10.3389/fcell.2021.705697. eCollection 2021.
Long non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.
RT-qPCR and fluorescence hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both and . RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.
We observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.
The study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.
长链非编码RNA（lncRNAs）已被表明在胃癌（GC）的肿瘤发生和进展中起关键作用。然而，它们在胃癌中的作用仍有待进一步阐明。
采用逆转录定量聚合酶链反应（RT-qPCR）和荧光杂交（FISH）检测lncRNA NEAT1在胃癌组织和细胞系中的表达。进行基因集富集分析（GSEA）以筛选出NEAT1可能参与的潜在表型和途径。构建NEAT1沉默的AGS和MGC803细胞，并进行一系列功能实验以研究NEAT1在胃癌血管生成中的作用。利用RNA下拉和荧光素酶报告基因检测来阐明NEAT1在胃癌中发挥功能的机制。
我们观察到NEAT1在大多数胃癌标本和细胞系中上调。NEAT1高表达与胃癌患者的不良预后相关。实验表明，NEAT1通过增强内皮细胞的增殖、迁移和管形成能力促进胃癌血管生成。机制研究表明，NEAT1可以竞争性结合直接靶向TGFβR2的miR-17-5p。随后，通过上调一系列经典的促血管生成因子，特别是血管内皮生长因子（VEGF）来激活TGFβ/Smad通路。
该研究揭示了LncRNA NEAT1/miR-17-5p/TGFβR2轴是胃癌血管生成的一种新机制。破坏这一轴可能是胃癌治疗的一种潜在策略。
