FNDC3B Circular RNA Promotes The Migration And Invasion Of Gastric Cancer Cells Via The Upregulation Of CD44 Expression

Objects:CircRNAs are a new class of RNAs by the direct ligation of 5’ and 3’ends of linear RNAs.Many studies have demonstrated that these RNA molecules play an indispensable role in human cancer.However,the biological function of circRNAs in gastric cancer remain largely unknown.In this study,results found that the expression level of FNDC3B circular RNA(circFNDC3B)was decreased in gastric cancer tissues.It is speculated that circFNDC3B plays an important role in the development of gastric cancer.This study used two different gastric cancer cells with different levels of circFNDC3B as the main research object to explore the specific molecular mechanism of circFNDC3B in the development of gastric cancer.Methods:First,qRT-PCR was used to verify the expression of circFNDC3B in clinical samples of gastric cancer and gastric cancer cell lines.Secondly,the circFNDC3B overexpression vector using Gibson Assembly DNA cloning technology and siRNAs interference were used to explore the role of circFNDC3B in MGC-803 cells and BGC-823 cells respectively.A series of assays including western blot,wound-healing assay,transwell assay and qRT-PCR assay were used to investigate the role of circFNDC3B in gastric cancer cells.Finally,RNA-binding protein immunoprecipitation analysis(RIP)and RNA pull-down assay were performed to confirm the interaction between the relationship of circFNDC3B,IGF2BP3 and CD44 mRNA.Results:Ectopic expression of circFNDC3B enhanced cell migration and invasion via inhibiting E-cadherin protein level,whereas silencing of circFNDC3B reduced the rate of cell migration and invasion via promoting E-cadherin protein level.In addition,circFNDC3B could promote the expression of CD44 protein and mRNA levels to affect cell adhesion and motility and then regulate cell migration and invasion.RIP and RNA pull-down assay demonstrated that circFNDC3B interacts with IGF2BP3 and CD44 mRNA to form circFNDC3B-IGF2BP3-CD44 mRNA ternary complex.Normally,IGF2BP3 interacts with CD44 mRNA to enhance its stability.Ectopic expression of circFNDC3B failed to recover the expression of CD44 when IGF2BP3 were silenced,which indicates that circFNDC3B binds to IGF2BP3 to promote CD44 expression.Conclusion:CircFNDC3B can affect the migration and invasion of gastric cancer cells in two ways.First,circFNDC3B inhibits the expression of E-cadherin and promotes migration and invasion of EMT transition.Second,circFNDC3B interacts with IGF2BP3 and CD44 mRNA to form circFNDC3B-IGF2BP3-CD44 mRNA ternary complex can increase CD44 expression,thereby promoting cell migration and invasion.Finally,this study believe that circFNDC3B can be used as a marker for the diagnosis of early gastric cancer,and be used as a targeting molecule to treat malignant differentiation of gastric cancer and inhibit the progression of gastric cancer in late gastric cancer.