Abstract
BackgroundCircular RNA downstream neighbor of SON (circDONSON) has been revealed to promote gastric cancer (GC) growth and invasion, while the role and molecular mechanism underlying circDONSON in GC cisplatin (DDP) resistance remain unclear.MethodsLevels of circDONSON, microRNA (miR)-802, and B lymphoma Mo-MLV insertion region 1 (BMI1) mRNA were detected using quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit-8 assay, colony formation assay and flow cytometry, respectively. Protein levels of BMI1, Cyclin D1, p27, Caspase-3 Cleavage and Caspase-9 Cleavage were determined by western blot. The interaction between miR-802 and circDONSON or BMI1 was confirmed by dual-luciferase reporter assay. In vivo experiments were conducted via the murine xenograft model.ResultsCircDONSON was elevated in GC tissues and cell lines, especially in DDP-resistant GC tissues and cells. Knockdown of circDONSON sensitized GC cells to DDP by inhibiting cell viability and promoting cell apoptosis in vitro. Further mechanism-related investigations suggested that circDONSON functioned as “sponge” by competing for miR-802 binding to modulate its target BMI1. Silencing miR-802 reversed the inhibition of DDP-resistance in GC cells induced by circDONSON down-regulation. Besides, miR-802 alleviated DDP resistance in GC cells by targeting BMI1. Functionally, circDONSON knockdown enhanced the cytotoxicity of DDP in GC in vivo.ConclusionOur findings demonstrated circDONSON promoted cisplatin resistance in gastric cancer cells by regulating miR-802/BMI1 axis, shedding light on the development of a novel therapeutic strategy to overcome chemoresistance in gastric cancer patients.
Highlights
Circular RNA downstream neighbor of SON has been revealed to promote gastric cancer (GC) growth and invasion, while the role and molecular mechanism underlying circDONSON in GC cisplatin (DDP) resistance remain unclear
It was found circDONSON was increased in GC cell lines (AGS and HGC-27) relative to gastric
CircDONSON knockdown inhibits DDP resistance of GC cells in vitro It had been proved that circDONSON was elevated in DDP-resistant GC tissues and cells, further cellular experiments were carried out to investigate the action of circDONSON on DDP resistance in GC cells
Summary
Circular RNA downstream neighbor of SON (circDONSON) has been revealed to promote gastric cancer (GC) growth and invasion, while the role and molecular mechanism underlying circDONSON in GC cisplatin (DDP) resistance remain unclear. Liu et al Cancer Cell Int (2020) 20:261 great significance to better understand the underlying mechanisms of DDP resistance in gastric cancer. Circular RNA downstream neighbor of SON (circDONSON) is novel identified circRNA, which is derived from back-splicing of DONSON mRNA. Ding et al demonstrated that circDONSON expression was elevated in gastric cancer, and high circDONSON expression was closely associated with unfavorable prognosis; importantly, knockdown of circDONSON significantly inhibited tumor growth in vivo and suppressed malignant biological behaviors of gastric cancer cells in vitro [11]. Whether circDONSON serves as a useful circRNA for intervening DDP resistance in gastric cancer has not been well investigated
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