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  • Title: Long noncoding RNA NEAT1 promotes the growth of gastric cancer cells by regulating miR-497-5p/PIK3R1 axis.
    Author: Xia TF, Chen J, Wu K, Zhang J, Yan Q.
    Journal: Eur Rev Med Pharmacol Sci; 2019 Aug; 23(16):6914-6926. PubMed ID: 31486491.
    Abstract:
    OBJECTIVE: To investigate the molecular mechanisms of long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC) development progress. MATERIALS AND METHODS: Relative mRNA and protein expression levels were quantified by quantitative Reverse Transcription-PCR (qRT-PCR) or Western blot analysis. Cell proliferation and cell apoptosis were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry, respectively. Binding sites of miR-497-5p on NEAT1 or phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were determined by RNA pull-down assay or dual-luciferase reporter assay. Finally, the tumorigenic role of NEAT1 in GC was assessed using a xenograft model on nude mice. RESULTS: NEAT1 was upregulated in GC tissues, promoted proliferation, and inhibited apoptosis of GC cells. NEAT1 could directly bind to and negatively regulate miR-497-5p expression. PIK3R1 was then identified as a downstream target of miR-497-5P. In GC cell models, PIK3R1 was found to be directly negatively regulated by miR-497-5p and indirectly positively regulated by NEAT1. Finally, NEAT1 knockdown inhibited tumor growth, increased miR-497-5p expression, and decreased PIK3R1 expression in xenograft model mice compared with the negative control. CONCLUSIONS: Functioned as an oncogene, NEAT1 promoted cell growth in GC by regulating miR-497-5p/PIK3R1 axis. These results provided valuable insights into the underlying regulation signaling in gastric cancer development, shedding light on NEAT1 a promising therapeutic target from bench to clinic.
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