MiR-144-5p And MiR-451a Inhibit Cell Growth Of Cholangiocarcinoma Through Targeting ST8SIA4 And Its Mechnism

Objective:By detecting the expressions of miR-144-5p and miR-451 a in paired bile duct carcinoma tissues and normal bile duct tissues and exploring the regulatory effects of miR-144-5p and miR-451 a on ST8SIA4,the relationship between miR-144-5p,miR-451 a and ST8SIA4 might have possible significance in the occurrence and development of cholangiocarcinoma.Methods:Through next-generation sequencing technology,we choose seven pairs of cholangiocarcinoma(ICC=3;HCCA=4)and matched to normal bile duct tissues to generate the cholangiocarcinoma miRNA profiles.Verification of cholangiocarcinoma miRNA profiles had already been completed by quantitative RT-PCR in 23 pairs of cholangiocarcinoma tissues as well as normal bile duct tissues.The clinical outcomes associated with miR-144-5p and miR-451 a expression levels were correlated in 98 patients.The influence of miR-144-5p and miR-451 a on CCA were analyzed both in vitro and in vivo,including proliferation,invasion,and metastasis.Luciferase reporter assays were carried out to verify whether miR-144-5p and miR-451 a could be capable of binding to the 3? untranslated regions of ST8SIA4 and decrease its translation.The biological effect of ST8SIA4 in cholangiocarcinoma cells was evaluated.Result:miR-144-5p and miR-451 a were significantly decreased in cholangiocarcinoma tissues and cells.This downregulation of miR-144-5p and miR-451 a was correlated with HBs Ag level,tumor size,histological classification and vascular invasion of cholangiocarcinoma.Overexpression of miR-144-5p and miR-451 a could suppress the capacities of invasion,migration and proliferation of CCA cells both in vitro and vivo.The increased expression of miR-144-5p and miR-451 a could decreased the expression of ST8SIA4,a target gene both of miR-144-5p and miR-451 a in cholangiocarcinoma cells.Overexpression of ST8SIA4 promoted cholangiocarcinoma cell proliferation,invasion and migration in vitro.Conclusion:Our results indicate that miR-144-5p and miR-451 a inhibit cell growth of cholangiocarcinoma through targeting ST8SIA4.