MiR-125a-5p Inhibits Invasion And Metastasis Of Gastric Cancer By Targeting BRMS1 Expression

Objective : Micro RNA 125a-5p(miR-125a-5p)has been reported to be a tumor suppressor in several types of cancer.Investigate the relationship between the expression of miR-125a-5p and clinical pathological characteristics of gastric cancer patients.Demonstrated miR-125a-5p regulated BRMS1 expression in GC and we hoped that those might expand our knowledge of GC tumorigenesis.Matedals and Methods: In order to do the research,we select two kinds of normal gastric mucosal cell line(GES1,HFE145)and 4 different malignant gastric cancer cell lines(SGC7901,HGC27,MKN28,BGC823).At the same time,82 cases of patients with gastric cancer in February 2010 to November 2012 at the First Affiliated Hospital of Nanchang University who underwent radical surgery of normal gastric tissues,gastric carcinoma,gastric cancer metastasis and clinical pathological data were collected.Clinicopathological data including: age,sex,tumor diameter,tumor location,degree of differentiation,lymph node metastasis,peritoneal metastasis and TNM staging.Using the method of Real-time quantitative PCR,one can measure the expression levels in various cell lines and the miR-125a-5p in different tissues;and using a variety of statistical methods,one can analyze the relationship between miR-125a-5p expression and the clinicopathological features.Besides one can draw survival curve analysis of miR-125a-5p expression levels on the prognosis of patients.Invasion and migration experiments show that the expression level of miR-125a-5p affect the invasion and migration of gastric cancer cells.Biology software predicts the gene BRMS1 as the target genes of miR-125a-5p,luciferase experiments has also proved the existence of binding sites between the two.Western-Blot experiment determined the expression levels of gastric cancer tissues and cells BRMS1.Results: The result of Real-time quantitative PCR showed that the expression of miR-125a-5p in gastric cancer cell lines and gastric cancer tissues is reduced compared with normal gastric cell lines and normal gastric tissue.Clinical pathology statistical analysis showed that the expression level of miR-125a-5p has significant difference with lymph node metastasis of gastric cancer(P=0.034),peritoneal metastasis(P= 0.030)and TNM stage(P= 0.025).but with no significant differences with age,gender,tumor size and location.The results of the survival curve proved that the higher expression of miR-125a-5p in patients,the longer-term patients can survival(P = 0.0092).Luciferase Shape prove the existence of a corresponding binding site between m RNA miR-125a-5p and BRMS1.Western-Blot test results show BRMS1 protein expression in gastric cancer cells is regulated by the level of miR-125a-5p: increasing the regulation of expression of miR-125a-5p in gastric cancer cells(SGC7901 and HGC27),BRMS1 protein levels increased;reducing the expression of miR-125a-5p in gastric cancer cells(BGC823),BRMS1 protein levels also decreased.Invasion and migration experiments confirmed the expression level of miR-125a-5p impact the invasion and migration of gastric cancer cells,and play a role by the pathway of miR-125a-5p-BRMS1.Conclusions:(1)The expression level of miR-125a-5p was associated with lymph node metastasis,peritoneal dissemination and advanced TNM stage,and affected overall survival rates of GC patients.(2)MiR-125a-5p regulated BRMS1 protein expression and impacted the invasion and migration of gastric cancer cells.