Stathmin Gene Silencing Suppresses Proliferation,Migration And Invasion Of Gastric Cancer Cells Via AKT/SCLU And STAT3 Signaling

Globally,gastric cancer is the fifth most common malignancy,it is one of the most common malignant tumors.The high mortality rate and poor prognosis of gastric cancer are closely related to its profound invasiveness,high incidence of metastases,rapid proliferation,and high rate of recurrence.Previous studies have confirmed that stathmin plays an important role in the occurrence,development and prognosis of gastric cancer.However,the detailed mechanisms by which stathmin affects these processes remain unclear.In this study,we used the relative and absolute quantitative techniques of isotopic labeling to search for proteins related to the effect of stathmin on gastric cancer,and then to explore the molecular mechanism of stathmin in the carcinogenesis and development of gastric cancer.Firstly,the differential expression of stathmin in gastric cancer and paracancerous tissues was examined by tissue microarray immunohistochemical staining.Then the expression of stathmin was down-regulated in AGS and MKN-28 gastric cancer cells by STMN-specific siRNA,and we further observed the biological functions of gastric cancer cells.The secretory proteins with or without stathmin knockdown were collected to study the quantitative proteomics by using itraq and mass spectrometry,we screened out the differentially expressed proteins.western blot and real-time quantitative pcr were used to verify the differential expression of these proteins in order to explore the possible molecular mechanism of the effect of stathmin on gastric cancer.Our data showed that stathmin was overexpressed in gastric cancer tissues,and that the migration,invasion and proliferation of gastric cancer cells decreased and apoptosis increased after the down-regulation of stathmin expression.A total of 96 differentially expressed proteins were screened by itraq and mass spectrometry,of which 45 proteins were significantly up-regulated and 51 proteins down-regulated.By Western blotting and real-time quantitative pcr assay,the differential expression of the proteins such as sCLU,CST3,CTSD,MMP1,MMP9,CDK1,HSP90,SOD1 were verified.According to the results of mass spectrometry and literature retrieval,the activity of pathway proteins such as AKT and STATs was further verified.It was found that the inhibition of stathmin expression decreased the activity of pathway proteins such as AKT and STATs.In this study,we verified that the high expression of STMN in gastric cancer tissues,and the differential expression of STMN in gastric cancer cells can significantly affect the biological function of gastric cancer cells.And we found that the inhibition of STMN decreased the activity of AKT and STATs in gastric cancer cells,which may lead to the decrease of the expression levels of Clusterin,Cystatin C and MMPs in gastric cancer cells,that conducted to the proliferation,migration and invasion of gastric cancer cells will be weakened.