Investigation Of The Functions And Mechanisms Of Long Noncoding RNA SNHG12 In Gastric Cancer

Background Gastric cancer(GC)is a common malignant tumor of the digestive system.Besides,it is the fifth most commonly-diagnosed cancer type and the third leading cause of cancer mortality worldwide.Although recent technological advances in early detection and treatment have partially improved the overall survival of patients with GC,the prognosis for patients with advanced GC still remains poor due to the high frequency of metastasis and recurrence.Therefore,it is particularly important to further study the mechanisms of gastric cancer and improve its early diagnosis and treatment.Recently,increasing evidence demonstrates that long noncoding RNAs(lnc RNAs)play critical roles during the initiation and progression of human cancers.However,the functions and mechanisms of lnc RNAs in GC still remain largely unknown.Methods Through analyzing the publicly available RNA sequencing data downloaded from Gene Expression Omnibus(GEO)of gastric cancer tissues,we identified a novel lnc RNA,small nucleolar RNA host gene 12(SNHG12).Then we analyzed the corrections of SNHG12 with GC clinic-pathological factors and prognosis using the datasets of The Cancer Genome Atlas(TCGA)and Kaplan-Meier plotter.Subsequently,The effects of SNHG12 on gastric cancer were investigated through a series of assays in vitro and in vivo,including RNA fluorescence in situ hybridization(FISH),cell counting kit-8(CCK-8)assay,colony formation assay,wound-healing assay,Transwell migration and invasion assay,apoptosis and cell cycle analysis,and the xenograft model.Then,a cancer pathway microarray,bioinformatic analysis,western blot,and immunohistochemistry were carried out to explore the mechanisms of SNHG12 on gastric cancer.Results Our analyses revealed that SNHG12 was upregulated in human gastric cancer tissues compared with the para-cancer tissues,and high SNHG12 expression was correlated with reduced patient survival.Besides,we found that the expression level of SNHG12 was associated with the tumor invasion depth of GC.The multivariate Cox regression model demonstrated that SNHG12 was an independent risk factor for GC.In vitro and in vivo functional experiments revealed that,knockdown of SNHG12 in AGS and MGC-803 cells inhibited GC cell proliferation,migration and invasion,and induced cell apoptosis and cell cycle arrest.On the contrast,overexpression of SNHG12 in BGC-823 cells had the opposite effects.Mechanistic investigations demonstrated that SNHG12 promoted the development of gastric cancer by activating the PI3K/AKT pathways.Conclusions Taken together,the results of our studies preliminarily illuminate the oncogenic functions and mechanisms of SNHG12 in gastric cancer,and suggest that SNHG12 may serve as a potential target for gastric cancer diagnosis and prognosis.