The Role And Mechanism Of HAVCR1 And PLCE1 In Hepatocellular Progression

Hepatocellular carcinoma(HCC)is one of the most malignant tumors with high incidence rate and mortality rate endangering Chinese people's health.It has been reported that metastasis is the important cause of the liver cancer death.However the mechanism of liver cancer metastasis remains unclear.So it is important to identify the mechanism of hepatocellular carcinoma metastasis.Moreover,due to lack of early biomarkers,two years of the recurrence rate is as high as 70%.Thus,identifying a prognostic biomarker is of far-reaching clinical significance for patients outcome with hepatocellular carcinoma.This thesis will focus on these important issues.HAV virus receptor protein(HAVCRI)is associated with the tumor development,however,the role of HAVCRI in hepatocellular carcinoma and whether HAVCR1 promotes the metastasis of hepatocellular carcinoma remain largely elusive.Here we show that the HAVCRI mRNA and protein levels were enhanced significantly under hypoxia in hepatocellular carcinoma cells.HAVCRI mRNA and protein levels have higher expression in clinical HCC patient samples compared with normal adjacent tissues.Mechanistically,our data demonstrate that HIF1? and HIF2? enhance HAVCR1 protein expression under hypoxia.Furthermore,we find that the wound healing capacity is significantly increased in the HCC cells with highly expressed HAVCR1.Interestingly,we find knockdown of HAVCRI significantly abolishs EMT marker expression under hypoxia.Therefore,our results indicate that HIF1a/HIF2a-regulated HAVCRI may paly important roles in the metastasis of liver cancer cells.In addition,previous studies have demonstrated that the role of phospholipase Cs l(PLCE1)is specific in cancer,but its function and clinical significance in hepatocellulsar carcinoma is not clear.Compared with corresponding adjacent tissues,phospholipase C epsilon l(PLCEl)mRNA and protein levels are decreased in human hepatocellular carcinoma tissues.Then we analyze the correlation,between PLCEI levels and the patients pathological characteristics,and found that PLCE1 i5 negatively correlated with vascular invasion(P=0.006),tumor capsule(P=0.025),the AFP(P=0.011)and grade of Edmondson(P=0.009)and TNM staging(P=0.009).So the low expression of PLCE1 in HCC patients was a unfavorable factor for clinical outcome.In summary,our findings uncover the role of HAVCR1 in regulating hepatocellular carcinoma metastasis,and that PLCE1 is significantly associated with tumor progression in hepatocellular carcinoma.Thus,HAVCR1 and PLCE1 may provide a potential theoretical basis for cancer progression.