Study On The Mechanism Of Endoplasmic Reticulum Oxidase 1? Promoting Cell Migration And Invasion In Human Hepatocellular Carcinoma

Objective:ERO1? is an oxidase that exists in endoplasmic reticulum and plays a vital role in the synthesis of disulfide bonds of proteins.It has been reported that ERO1? is up-regulated in various types of cancers and cell lines.However,the expression and function of ERO1? in hepatocellular carcinoma have not been illustrated.In this study,we aimed to identify the expression and functional roles of ERO1? in the development and progression of HCC.Methods:The expression level of ERO1? was detected in HCC tissues and cell lines by quantitative real time PCR and Western blot.ERO1? stably knockdown cells were developed with short hairpin RNAs(shRNA).Stable overexpression of ERO1?cells were developed by overexpression lentivirus of ERO1?.Knockdown of S1PR1 in ERO1? overexpression cells was also performed by S1PR 1 siRNA.The effect of ERO1? on cell migration and invasion was studied in vitro.Nude mice model was used to explore the role of ERO1? in tumor migration and invasion in vivo.Regulatory mechanism of ERO1? in HCC was studied by qRT-PCR,Western blot,Transwell and Wound healing to identify the function of ERO1? in the migration and invasion of HCC.Results:We firstly found that ERO1? is significantly high expression in HCC tissues and cell lines.High expression of ERO1? is evidently associated with poor prognostic features and reduced survival of HCC patients.Loss and gain of function studies showed that ERO1? prompted the migration and invasion of HCC cell both in vitro and in vivo.In addition,we revealed that ERO1?-mediated promotion of migration and invasion is linked to S1PR1-STAT3 signaling by the regulation of S1PR1?Conclusion:ERO 1? plays a crucial role in the migration and invasion of HCC and can be acted as a biomarker for the prognosis factor of HCC.