Expression of endoplasmic reticulum oxidoreductase 1-α in cholangiocarcinoma tissues and its effects on the proliferation and migration of cholangiocarcinoma cells

ABSTRACT: Endoplasmic reticulum oxidoreductase 1-α (ERO1A) is a kind of hypoxia-induced endoplasmic reticulum oxidase that regulates translation and folding of oxidized proteins. This study aimed to explore the clinicopathological significance of ERO1A and the effect on the biological behavior of cholangiocarcinoma (CCA) cells. METHODS: Immunohistochemical staining was used to detect the expression of ERO1A, carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in cholangiocarcinoma. Immunofluorescence staining was performed to detect the subcellular localization of ERO1A in CCA cells. The expression of ERO1A in CAA cells after depletion or overexpression was verified by Western blot assay. Then, the effect of ERO1A on proliferation in CCA cells was verified by MTT assay and colony formation assay. Wound healing assays and migration assays were performed to detect the effect of ERO1A on cell migration ability. Finally, we explored the role of ERO1A in EMT and Akt/mTOR signaling pathway. RESULTS: In this study, our data demonstrated that ERO1A, CEA, and CA19-9 were expressed in cholangiocarcinoma tissues, and the positive rates were 95%, 95%, and 55%, respectively. The high expression of ERO1A is associated with clinical stage and pathological stage of CCA. In vitro data indicate that deletion of ERO1A can inhibit the proliferation and migration of CCA cells and vice versa. In addition, ERO1A has been shown to be closely related to EMT and Akt/mTOR pathways. CONCLUSION: In summary, we found that high expression of ERO1A is associated with poor prognosis in patients, and ERO1A can promote the proliferation and migration of CCA cells. In conclusion, ERO1A can be used as an independent biomarker for predicting the prognosis of CCA.