biostudies-literatureWang LNational Natural Science Foundation of China-Guangdong Joint FundGuangxi Zhuang Autonomous Region Health and Family Planning CommissionNational Natural Science Foundation of Chinae12981https://www.ebi.ac.uk/biostudies/studies/S-EPMC7941240biostudies-literatureUnknown54(3)<h4>Objectives</h4>Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC).<h4>Methods</h4>Gene 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.<h4>Results</h4>Circ_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.<h4>Conclusion</h4>Circ_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.Cell proliferationCirc_SMAD4 promotes gastric carcinogenesis by activating wnt/β-catenin pathway.PMC7941240S201407‐0481560402S201407-04Yi XMa LXiao XZheng QLi BWang LfalseCirc_SMAD4 promotes gastric carcinogenesis by activating wnt/β-catenin pathway.<h4>Objectives</h4>Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC).<h4>Methods</h4>Gene 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.<h4>Results</h4>Circ_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.<h4>Conclusion</h4>Circ_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.2021-01-01T00:00:00Z2021 Mar2025-04-18T13:42:27.688Z2025-04-06T23:28:24.811ZS-EPMC79412403345891710.1111/cpr.12981