Molecular Action Mechanism Of CircPTK2 Regulating The Proliferation And Metastasis Of Gastric Cancer Mediated By Sanguinarine

Backgroud: Circular RNAs(circ RNAs)are a novel class of endogenous nocoding RNAs formed by a covalently closed loop.Increasing evidence reveals that circ RNAs play crucial roles in regulating the gene expression of cancer.But,the molecular Action mechanisms of Sanguinarine(SAG)and circ RNAs in gastric cancer(GC)remain elusive.Methods: The differentially expressed hsa?circ?0006421(circ PTK2)was identified by a circ RNA expression profiling between GC cell and GC cell with Sanguinarine(SAG).The correlation of circ PTK2 or mi R-134-5p with clinicopathological characteristics and prognosis of GC patients was analyzed by q RT-PCR,FISH and TCGA data.CCK8,colony formation,Transwell and Ed U assays as well as subcutaneous xenograft tumor models and caudal vein pulmonary metastasis models were performed to assess the effcts of circ PTK2 on GC cell proliferation and invasion.Circ PTK2 specific binding with mi R-134-5p was verified by using RNA in vivo precipitation,dual luciferase gene report and rescue assays.The effects of circ PTK2 on mi R-134-5p expression and CELF2/PTEN signaling in GC cells were examind by q RT-PCR and Western blot analysis.Resuts: The expression of cric PTK2 was downregulated but mi R-134-5p expression was markedly upregualated in GC tissues as compared with the adjacent normal tissues.Low expression of circ PTK2 or high expression of mi R-134-5p was related to the poor survival or tumor recurrence in GC patients.Overexpression circ PTK2 suppressed the proliferation,colony formation,DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo,while silencing circ PTK2 exhibited the opposite effects.Moreover,circ PTK2 was negatively correlated and co-localized with mi R-134-5p in cytoplasm of GC tissue cells.circ PTK2 could bind with mi R-134-5p and act as its sponge in GC cells,while mi R-134-5p facilitated cell growth and invasion but attenuated circ PTK2 induced tumor suppressieve effects and CELF2/PTEN signaling activation in GC cells.Conclusions: Our studies demonstrated that hsa?circ?0006421(circ PTK2)functions as a tumor suppressor in GC by sponging mi R-134-5p and activating CELF2/PTEN axis and may offer a potential survival biomarker for patients with GC.Sanguinarine inhibits the biological behavior of gastric cancer by mediating the expression of circ PTK2.