The Mechanism Of LincNMR Regulating Gastric Cancer Cell Proliferation Via MiR-520b/RAB22A Axis

BackgroundGastric cancer is a common malignant tumor in the world,and its fatality rate ranks the third among all kinds of cancers.From the situation of the incidence of different regions,the incidence of different regions there are great differences.In China,gastric cancer ranks the second in the incidence and death.Although progress has been made in the discovery and exploration of the pathogenesis of gastric cancer as well as drug therapy,the overall survival rate of gastric cancer patients is still unsatisfactory.Therefore,the study of the molecular mechanism of gastric cancer and the search for new targets are of great significance for the diagnosis and treatment of gastric cancer.It is now widely believed that LincNMR dysregulation is closely related to various malignant biological behaviors in the development of cancer.However,significantly LincNMR and their important clinical significance in gastric cancer have not been reported yet.ObjectiveWe aim to investigate the potential roles and mechanisms of LincNMR in GC cells proliferation.Methods1.Patients and tissue speciments:all fresh gastric cancer tissue specimens and its matched normal gastric epithelial tissue with negative incisitive margin(surgical resection)used in the experiment were from gastric cancer patients in the People’s Hospital of Linzhou City Henan Province.Tissue RNA was extracted for further study.In addition,thirty-four paired fresh GC samples were collected from patients who underwent radical gastrectomy in Linzhou People’s Hospital from 2015 to 2019(each patient included tumor tissue and matched normal gastric mucosal epithelial tissue with negative incision-margin),the clinicopathological data and the prognostic follow-up data were combined.2.MethodsFour kinds of GC cell lines,including SGC 7901,BGC 823,MKN-45 and AGS,and one normal gastric epithelial cell line GES-1 were used for our study.The alteration of LincNMR in GC was first verified in TCGA database,and then further evaluated and analyzed in GC samples and cell lines.The clinical pathological information was analyzed for the association between LincNMR expression and OS.LincNMR overexpression and downregulation GC cell lines were used for functional and mechanistic studies.CCK-8 and colony formation assays were used for evaluating the proliferative capacity of LincNMR,and the oncogenic role of LincNMR was further evaluated in vivo in nude mice.The interaction among LincNMR,miR-520b and RAB22A were evaluated by RIP,qPCR,Western bolt and luciferase reporter assay.ResultsLincNMR was upregulated in GC and associated with poor prognosis.LincNMR promoted cell proliferation of GC cells in vitro and in vivo by sponging and reducing the inhibitory effect of miR-520b.Additionally,we identified that RAB22A is a direct target for miR-520b.Conclusion1.LincNMR could serves as an oncogenic lncRNA and as a prognostic biomarker for GC.2.Targeting LincNMR/miR-520b-RAB22A axis could be an effective method for GC intervention.