AUTHOR=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 TITLE=LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.705697 DOI=10.3389/fcell.2021.705697 ISSN=2296-634X ABSTRACT=Background

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.

Methods

RT-qPCR and fluorescence in situ 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 in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.

Results

We observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro 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.

Conclusion

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.