ST3GAL6 Mediates The Effect Of MiR-26a On Cell Growth,Migration And Invasion In Hepatocellular Carcinoma Via The Akt/mTOR Pathway

Objective: This study aimed to investigate the relationship between the alterations of ST3GAL6 and hepatocellular carcinoma(HCC),clarify the clinical significance of the alterations of ST3GAL6 in HCC and further investigate the detail mechanism of ST3GAL6 underling the regulation of HCC.The study would provide new therapeutic strategy and target to predict and diagnose HCC.Methods:(1)Q-PCR was used to measure the expression levels of ST3GAL6 in two types of HCC cell lines(MHCC97-H and MHCC97-L)and normal cell lines(LO2)and in tumor tissues and adjacent nontumor tissues.(2)The capacity of proliferation was measured using CCK8 asaay and colony formation assay while cell migration and invasion ability was detected using wound-healing assay and transwell invasion saasy.Analysis of a xenograft mouse model reveals the effects of miR-26 a and ST3GAL6/Akt/mTOR pathway on tumor growth in vivo.(3)Using network prediction softwares such as Miranda,Mibase,and TargetScan to predict the target miRNA of ST3GAL6.Luciferase assays were performed to verify the predict result of chosen miRNAs.(4)To detect the growth,migratory and invasive ability and the tumorigenicity of HCC both in vitro and in vivo,the differentially expression of miR-26 a and ST3GAL6 were regulated.(5)To test the effect of miR-26 a and ST3GAL6 on Akt/mTOR pathway,we used gain-of-function and loss-of-function analysis by silencing or over-expressingmiR-26 a or ST3GAL6,the altered activation of Akt/mTOR pathway was measured by western blot analysis.Results:(1)ST3GAL6 is up-regulated in human HCC tissues and cell lines.(2)ST3GAL6 regulates the invasion,migration and proliferation of HCC cells.(3)miR-26 a is a negative regulator of ST3GAL6.(4)miR-26 a suppresses the proliferation,migration and invasion of HCC cells by negatively regulating ST3GAL6.(5)ST3GAL6 mediates the regulation of miR-26 a via the Akt/mTOR signaling pathway.(6)miR-26 a suppresses tumor growth through ST3GAL6/Akt/mTOR pathway in vivo.Conclusion:(1)The expression of ST3GAL6 was different in MHCC97-H and MHCC97-L cells.The altered level of ST3GAL6 is correlated with the proliferation,migration and invasion capacity of HCC.(2)ST3GAL6 mediates the effect of miR-26 a on the proliferation,migration and invasion of HCC in vitro and tumor growth in vivo through the Akt/mTOR signaling pathway.