Study On The Mechanisms Of HBXIP Promoting Invasion And Metastasis In Hepatocellular Carcinoma

Part 1 Abnormal nuclear expression of HBXIP in human primary hepatocellular carcinoma correlates with a poor prognosisThe aim of the present study was to investigate the expression patterns and clinic pathological significance of HBXIP in human primary hepatocellular carcinoma(HCC).Real-time polymerase chainreaction(PCR)analysis of the mRNA levels of HBXIP in 61 paired HCC cancer/adjacent non-cancerous tissues indicate that HBXIP mRNA expression was significantly higher in cancerous tissues(P=0.0009).MRNA levels of HBXIP analysis showed that ectopically HBXIP mRNA expression in HCC patients was related to gender(P=0.031)and hepatic metastasis(P=0.047).Survival analysis showed that abnormal HBXIP expression was a risk factor associated with the prognosis of HCC patients(P=0.0146).Conclusion:As far as we know,this is the first report investigating HBXIP expression patterns and their clinicopathological significance in HCC.Part 2 HBXIP promotes invasion and metastasis of hepatic carcinoma cell by decreasing MMP15 expressionHBXIP has been ectopically expressed in several malignancies,such as ovarian and breast cancers.Despite our previous research has verified that HBXIP messenger RNA and protein is over-expressed in human liver cancerous tissues and associated with a poor prognosis of HCC patients,little is known about whether HBXIP could regulate Hepatic Carcinoma Cell invasion and metastasis.Our study validated that down-regulated HBXIP expression by ShRNA inhibits hepatic carcinoma cell invasion in vitro and metastasis in xenograft tumor models,which were effectively promoted when expression of HBXIP was over-expressed.Mechanistic study revealed that the capacity of HBXIP to positively regulate Hepatic Carcinoma Cell invasion and metastasis potency is mediated by repression of MMP15 expression,by binding promoter directly.So our finding demonstrates an pivotal role for HBXIP mediating the MMP15 expression as well as invasiveness in human Hepatic Carcinoma Cells.Hence,consideration of targeted suppression of HBXIP to inhibit metastasis of hepatic carcinoma is varified.