The discovery of
circular RNA (
circRNA) enormously complimented the repertoire of traditional gene expression theory. As a type of endogenous
noncoding RNA,
circRNA participates in the occurrence of many kinds of
tumors in addition to regulating their development. The Warburg effect (aerobic glycolysis is taken with priority for
cancer cells instead of oxidative phosphorylation) is one of the most important factors involved in the excessive proliferation of
gastric cancer cells. Our data showed that
circRNA circATP2B1 (also called hsa_circ_000826) was overexpressed in
gastric cancer tissues instead of linear ATP2B1
mRNA, and it promoted aerobic glycolysis in
gastric cancer cells. Bioinformatic Gene Ontology analysis showed that the potential downstream targets of circATP2B1 include the
microRNA miR-326 gene cluster (miR-326-3p/miR-330-5p), which is functionally focused on cell growth and metabolic processes. The expressions of miR-326-3p/miR-330-5p were downregulated in
gastric cancer, and circATP2B1 functionally targeted miR-326-3p/miR-330-5p in an
RNA-induced silencing complex (RISC) dependent manner. Dual-
luciferase reporter assays demonstrated that
pyruvate kinase M2 (PKM2) was one of the targets of miR-326-3p/miR-330-5p. As a rate-limiting
enzyme in the aerobic glycolytic pathway, PKM2 accelerated
gastric cancer cells'
glucose uptake and increased cell viability. Taken together, circATP2B1 captured miR-326-3p/miR-330-5p and decreased the suppression of PKM2 by miR-326-3p/miR-330-5p, thus aiding the aerobic glycolysis and proliferation of
gastric cancer cells. This study identified a novel molecular pathway in
gastric cancer that may provide more targets for reversing
cancer metabolic reprogramming, as well as a potential strategy for targeted
therapy of
gastric cancer.