Background: Circular RNAs (circRNAs) are a special kind of non-coding RNAs that are implicated in cancer malignant behavior, including glycolysis. However, their contributions to gastric cancer (GC) cell glycolysis are still poorly understood. In the present study, we aimed to investigate the glycolysis-related role of circ-MAT2B in GC.
Methods: Gene expression was determined by qRT-PCR analysis. Protein level was detected by Western blot. The CCK-8, colony and EdU assays were carried out to assess GC cell viability, colony formation and DNA synthesis rate. Glycolysis was determined by glucose uptake and lactate production. The positive regulatory network of circ-MAT2B/miR-515-5p/HIF-1α was identified by RNA pull-down, RIP, ChIP and luciferase reporter assays. The in vivo role of circ-MAT2B was evaluated by using xenograft tumor model.
Results: Circ-MAT2B was notably increased in GC and could be used as a sensitive and specific indicator of GC diagnosis and prognosis. Stable knockdown of circ-MAT2B dramatically inhibited GC cell viability, colony formation, DNA synthesis, glucose uptake and lactate production in vitro, and retarded tumor growth in vivo. Mechanistically, circ-MAT2B was dominantly located in the cytoplasm and acted as a ceRNA to sponge miR-515-5p and increase HIF-1α expression. Silencing of miR-515-5p or overexpression of HIF-1α could evidently rescue the attenuated aggressive phenotype of GC cells caused by circ-MAT2B knockdown. Importantly, HIF-1α was able to directly bind to circ-MAT2B promoter and transcriptionally activate circ-MAT2B, thus forming a positive feedback loop.
Conclusion: Our data suggest that circ-MAT2B is a oncogenic circRNA in GC and provide a promising therapeutic target for GC patients.
Keywords: Glycolysis; HIF-1α; circ-MAT2B; miR-515-5p.
© The Author(s) 2020.