| microRNAs (miRs) are short noncoding RNAs that post‐transcriptionally
suppress gene expression. miR‐146a acts as an oncogene or a tumor suppressor
in various cancers, including gastric cancer, but it is unclear what determines
whether miR‐146a is oncogenic or tumor suppressive and the molecular
mechanisms are still largely unknown. The aim of this study was to investigate
the role of miR‐146a in gastric cancer, by focusing on its expression in patients
who were negative for Helicobacter pylori and its reduced and increased
expression effect in vitro. Twenty gastric cancer patients who were negative for
H. pylori infection were selected and the expression levels of miRNA‐146a in
these gastric tumors, in their matched normal gastric tissues and in gastric
cancer cell lines with varying tumorigenic potential was measured. Further, the
impact of increased and decreased miR‐146a expression levels on the expression
of predicted target genes, cell migration, viability, proliferation, and apoptosis
was examined, respectively. Our results for the first time indicated that miR‐
146a is downregulated in H. pylori–negative gastric cancers and suggests that
H. pylori infection determines whether miR‐146a acts as an oncogene or tumor
suppressor. The level of miR‐146a expression inversely correlates with the
tumorigenicity of three gastric cancer cell lines and low miR‐146a expression
predicts poor recurrence‐free survival. It was also found that miR‐146a reduces
the expression levels of the prometastatic genes and suppresses MKN‐45 cell
migration. Functional studies showed that miR‐146a acts as a tumor suppressor
miR and identifies miR‐146a as a candidate for antimetastatic miRNA
replacement therapy for gastric cancer patients. |