The Role And Mechanism Of MiR-375 In Gastric Cancer

BackgroundGastric cancer is the second leading cause of cancer death worldwide,with a particularly high incidence in Asian countries including China and Japan.Despite the declining incidence of stomach cancer,more than 1 million new cases are diagnosed and 850,000 gastric cancer patients die each year worldwide.The high mortality rate of gastric cancer is mainly due to late clinical progression,since early gastric cancer is generally asymptomatic or mostly presents with non-specific symptoms.Survival depends on the stage of gastric cancer at the time of diagnosis.Therefore,it is urgent to find biomarkers for non-invasive early detection of gastric cancer patients.Abnormal expression of micro RNAs(mi RNAs)is a hallmark of the disease.Mi Rnas are endogenous non-coding Rnas that are involved in many biological processes(such as cell proliferation,differentiation,apoptosis,invasion and development)through gene inhibition.Mi RNA plays a key role in the biological processes of cell proliferation,metastasis,differentiation,development and apoptosis.mi RNA is stable and easily obtained from tissues,blood and ascites,which has the potential to be a biomarker in the diagnosis of gastric cancer.The abnormal expression of many mi RNA plays an important role in the occurrence and development of gastric cancer.mi R-375 plays an important role in a variety of diseases,including glioma,pancreatic cancer,and asthma.However,its role and mechanism in gastric cancer have not been fully elucidated.Therefore,the purpose of this study is to explore the effect of mi R-375 on the occurrence and development of gastric cancer and the specific molecular mechanism of its participation,so as to provide a new target for clinical diagnosis and treatment of gastric cancer.ObjectiveIn this study,the expression of mi R-375 in gastric cancer and its relationship with prognosis of patients were analyzed,and the effect of mi R-375 on gastric cancer and its molecular mechanism were explored,so as to provide a reliable theoretical basis and new direction for clinical diagnosis,treatment and prognosis evaluation of gastric cancer.MethodsThis study was mainly divided into three methods.Method 1: q PCR was used to analyze the expression difference of mi R-375 in gastric cancer tissues and adjacent tissues.TGCA database was used to analyze the relationship between mi R-375 expression and patient prognosis,and to explore the expression and clinical correlation of mi R-375 in gastric cancer.Method 2: The effects of mi R-375 knockdown on the proliferation,apoptosis,invasion and metastasis of gastric cancer cells were analyzed by si RNA knockdown in cell lines with high mi R-375 expression,and the biological functions of mi R-375 were analyzed.Method 3: sh RNA was used to knock down mi R-375 in cell lines with high mi R-375 expression,and the effect of mi R-375 knockdown on the activation of JAK/STAT signaling pathway in gastric cancer cells was analyzed,and the biological mechanism of mi R-375 influence on the occurrence and development of gastric cancer was explored.ResultsIn this study,the expression differences of mi R-375 in gastric cancer tissues and corresponding adjacent tissues were detected by q PCR.the results showed that the expression of mi R-375 in gastric cancer was significantly increased compared with normal adjacent tissues,and the difference was further increased with the change of TNM stage(P< 0.05).we analyzed the expression of mi R-375 in gastric cancer tissues and corresponding adjacent tissues through TCGA database.Compared with the patients with low mi R-375 expression,the survival time(PFS and OS)of the patients with high mi R-375 expression was significantly shorter(P < 0.05).Mi R-375 knockdown could significantly inhibit the proliferation of gastric cancer cell SGC-7901,significantly promote the apoptosis of gastric cancer cell SGC-7901,and significantly inhibit the invasion and metastasis of gastric cancer cell SGC-7901(P <0.05).Down-regulation of mi R-375 can inhibit the expression of SGC-7901 JAK protein and significantly reduce the phosphorylation level of STAT3 protein in gastric cancer cells.mi R-375 knockdown can significantly increase the proliferation and metastasis of gastric cancer SGC-7901 cells,but overexpression of JAK can reverse the biological activity of mi R-375 knockdown.ConclusionIn this study,we found that mi R-375 is highly expressed in gastric cancer and negatively correlated with the prognosis and survival time of patients,which may be related to the involvement of mi R-375 in the regulation of the occurrence and development of gastric cancer.Through in vitro cell experiments and in vivo transplanted tumor models,we proved that mi R-375 can activate the JAK/STAT3 signaling pathway to promote the proliferation,survival,invasion and metastasis of gastric cancer cells,inhibit cell apoptosis.Therefore,mi R-375 can be used as a new target for clinical treatment of gastric cancer.