Abstract
BackgroundLong 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.MethodsRT-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.ResultsWe 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.ConclusionThe 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.
Highlights
Gastric cancer is the fifth most frequent malignancies and the fourth leading cause of cancer death globally
In GSE66229 cohort, we found that nuclear-enriched abundant transcript 1 (NEAT1) was significantly highly expressed in gastric cancer (GC) compared with normal gastric tissues (Figure 1A)
To verify NEAT1’s potential roles in GC angiogenesis, we firstly detected the secretion of VEGF, a key secretory protein in regulating tumor vascularization, in the culture medium (CM) of GC cells with different NEAT1 expression levels through Enzyme-Linked Immunosorbent Assay (ELISA) assays
Summary
Gastric cancer is the fifth most frequent malignancies and the fourth leading cause of cancer death globally. In spite of the remarkable progression in diagnoses and therapies, overall prognosis of GC patients remains dismal (Siegel et al, 2021). Developing effective targeted therapies for successful intervention is vitally important. Excessive angiogenesis is widely believed to fuel tumor. LncRNA NEAT1 Promotes Gastric Cancer Angiogenesis proliferation and metastases, and is identified as a hallmark accounting for the poor prognosis of GC. Anti-angiogenic therapy has raised more and more interest due to its low response rate and the inevitable chemoresistance. Long non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. Their roles in GC remain to be further elucidated
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