Circ_SMAD4 promotes gastric carcinogenesis by activating wnt/β-catenin pathway.

Abstract

ObjectivesCircular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC).MethodsGene expression was detected by qRT‐PCR or Western blot. Survival curves were generated via Kaplan‐Meier method. In vitro and in vivo assays were used to investigate the impact of circ_SMAD4 on GC cell growth and tumorigenesis. Agarose gel electrophoresis assay, RNase R treatment and Sanger sequencing were utilized for confirming the circular structure of circ_SMAD4. Relationship between molecules was monitored by a series of mechanical experiments, as needed.ResultsCirc_SMAD4 expression was potentiated in GC. Circ_SMAD4 depletion impeded GC cell growth in vitro and restrained tumorigenesis in vivo. Mechanically, nuclear circ_SMAD4 recruited TCF4 to facilitate CTNNB1 transcription, while cytoplasmic circ_SMAD4 sequestered miR‐1276 to prevent the silence of CTNNB1 mRNA, leading to activation of Wnt/β‐catenin pathway. Rescue experiments validated that circ_SMAD4 depended on miR‐1276/TCF4‐regulated CTNNB1 to elicit accelerating effects on GC cell growth.ConclusionCirc_SMAD4 facilitated GC tumorigenesis by activating CTNNB1‐dependent Wnt/β‐catenin pathway. Hopefully, the findings could provide new clues for improving GC prognosis and treatment.