Background: Radioresistance is a major obstacle for clinical treatment of gastric cancer (GC). has_circ_0003506 (circ_0003506) was reported as an oncogenic factor in GC, but its effect on radioresistant GC is unclear.
Aims: This study aimed to explore the role of circ_0003506 in radioresistance and regulatory mechanism.
Methods: The expression detection was performed by real-time polymerase chain reaction. Cell survival was analyzed by colony formation assay. Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assay. Cell migration and invasion were examined using transwell assay. Cell apoptosis was assessed by flow cytometry. The target binding was confirmed via dual-luciferase reporter assay. The protein level was determined through western blot. Animal assay was performed for the functional exploration of circ_0003506 on radiosensitivity in vivo.
Results: Circ_0003506 was upregulated in radioresistant GC cells. Downregulation of circ_0003506 inhibited radioresistance to repress proliferation, migration and invasion but increase apoptosis in radioresistant GC cells. Circ_0003506 was a sponge of miR-1256. The effects of si-circ_0003506 on radioresistant GC cells were reverted by miR-1256 inhibitor. MiR-1256 suppressed tumor progression in radioresistant GC cells by downregulating bone morphogenetic protein type 2 receptor. Circ_0003506 regulated the level of bone morphogenetic protein type 2 receptor by targeting miR-1256. Downregulating circ_0003506 increased radiosensitivity of GC in vivo via regulating miR-1256 and bone morphogenetic protein type 2 receptor.
Conclusion: Knockdown of circ_0003506 suppressed radioresistance in GC through the regulation of miR-1256/bone morphogenetic protein type 2 receptor axis. Circ_0003506 might be a therapeutic target in radiotherapy of GC.
Keywords: BMPR2; Circular RNA; MicroRNA; Radioresistance; Stomach neoplasms.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.