Effects Of MiR-194 On Self-renewal,Migration,Invasion And Gemcitabine Resistance Of Gallbladder Cancer Cells

Objective:To analyze the effect of miR-194(microRNA 194)on the self-renewal,migration and invasion of gallbladder cancer cells,and to observe how the miR-194 expression affects gallbladder cancer cells’ resistance to gemcitabine.Methods:1.CD44 and CD 133 positive gallbladder cancer stem cells were screened out from SGC-996 and GBC-SD cell lines by Flow Cytometry.The expression level of miR-194 was compared with that of CD44 and CD 133 negative cells.2.To investigate the effect of miR-194 expression on the self-renewal and invasion of SGC-996 and GBC-SD cells.3.To change the expression level of miR-194 in gallbladder cancer cell lines SGC-996 and GBC-SD by construction of plasmid vector.4.To find out the relationship between miR-194’s expression with the expression ratio of CD44 and CD133 in SGC-996 and GBC-SD cell lines.5.The relationship between miR-194 and SOX4(SRY-related HMG-BOX 4)was analyzed.6.The sensitivity to gemcitabine was compared between miR-194 overexpression group and control group.Results:1.The expression level of miR-194 in gallbladder cancer stem cells decreased significantly.2 Overexpression of miR-194 significantly reduced the ablitity of self-renewal,migration and invasion of gallbladder cancer cells,while down regulation of miR-194 enhanced the proliferation,migration and invasion of these cells.3.Overexpression of miR-194 significantly decreased the expression of CD44 and CD 133 in,while down regulating miR-194 expression,the expression of CD44 and CD 133 increased significantly in SGC-996 and GBC-SD cells..4.MiR-194 was antagonistic to SOX45.Under the same dose of gemcitabine(10μmol/L),the apoptosis rate of gallbladder cancer cells increased significantly when the miR-194 was overexpressedConclusion:The expression level of miR-194 was negatively correlated with the self-renewal,migration and invasion of gallbladder cancer cells.Furthermore,overexpression of miR-194 Weakened its stem cell characteristics.MiR-194 could antagonize the effect of SOX4,and increase sensitivity of gallbladder cancer cells to gemcitabine,which provided the basis for the next step to study the relationship between miR-194 and prognosis of gallbladder cancer patients,to find out the regulatory mechanism involved in developing targeted drugs for gallbladder cancer treatment.