HuR Promotes The Progression Of Gastric Cancer By Mediating CDC5L Expression

Objective:Gastric cancer(GC)is one of the most common tumors in the gastrointestinal tract and ranks the third in tumor mortality.Currently,lymph node metastasis is considered one of the most important prognostic factors affecting patients with gastric cancer;however,the mechanism of metastasis in gastric cancer is not fully understood and there are no specific predictors.Human antigen R(HuR),also known as embryonic lethal abnormal visual-like protein 1(ELAVL1),is an RNA binding protein(RBP).HuR has been found to be associated with the occurrence,invasion,metastasis and prognosis of hepatocellular carcinoma,esophageal squamous cell carcinoma,glioma,breast cancer,lung cancer and colorectal cancer.Some studies have shown that HuR is associated with the malignancy of gastric cancer.The aim of this study was to investigate the relationship with gastric cancer.Methods:1.The expression of HuR m RNA in 80 GC tissues and paraneoplastic tissues was analyzed by q RT-PCR.2.The possible relationship between HuR expression and survival of GC patients was investigated by Kaplan-Meier survival analysis.3.HuR protein expression levels in GC tissues and adjacent normal tissues were detected by Western blot.4.The cell models of SGC-7901 and MGC-803 of si-HuR were established to investigate their functions.5.The effects of HuR and miR-133 b on GC cells were examined by CCK8,cell colony formation and cell scratch assay.6.The effects of si-HuR on the cell cycles of SGC-7901 and MGC-803 were analysed by flow cytometry.7.A mouse tumor model was constructed to analyze the impacts of HuR on GC in vivo.Results:1.The expression of HuR was elevated in GC tissues from patients compared to normal tissues,and the expression of HuR was similarly ascended in GC cells compared to normal cells.2.Si-HuR inhibited the cell proliferation,migration and cell cycle in GC cells.3.Si-HuR inhibited the growth of tumor cells through mouse model analysis in vivo.4.HuR is the target gene of miR-133 b from Dual luciferase reporter assay.Overexpression of miR-133 b can inhibit the ability of proliferation and clone formation in GC cells.5.Si-HuR reduced CDC5 L expression in GC cells.Conclusions:The miR-133b-HuR-CDC5 L axis is involved in the growth process of GC cells.It can regulate GC cell proliferation,migration and cell cycle.