N6-Methyladenosine (m6A) is the most common posttranscriptional modification of
RNA and plays critical roles in
cancer pathogenesis. However, the biological function of
long noncoding RNA (
lncRNA) methylation remains unclear. As a demethylase, ALKBH5 (alkylation repair homolog
protein 5) is involved in mediating methylation reversal. The purpose of this study was to investigate
lncRNA m6A modification and its role in
gastric cancer (GC). Bioinformatics predicted interactions of ALKBH5 with lncRNAs. Five methods were employed to assess the function of nuclear paraspeckle assembly transcript 1 (NEAT1), including gene silencing, RT-PCR, separation of nuclear and cytoplasmic fractions, scrape motility assays, and transwell migration assays. Then,
m6A RNA immunoprecipitation and immunofluorescence were used to detect methylated NEAT1 in GC cells. Rescue assays were performed to define the relationship between NEAT1 and ALKBH5. NEAT1 is a potential binding
lncRNA of ALKBH5. NEAT1 was overexpressed in GC cells and tissue. Additional experiments confirmed that knockdown of NEAT1 significantly repressed invasion and
metastasis of GC cells. ALKBH5 affected the
m6A level of NEAT1. The binding of ALKBH5 and NEAT1 influences the expression of EZH2 (a subunit of the polycomb repressive complex) and thus affects GC invasion and
metastasis. Our findings indicate a novel mechanism by which ALKBH5 promotes GC invasion and
metastasis by demethylating the
lncRNA NEAT1. They may be potential therapeutic targets for GC.