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

Authors Yan W, Wang X, Liu T, Chen L, Han L, Xu J, Jin G, Harada K, Lin Z, Ren X

Received 26 September 2018

Accepted for publication 13 June 2019

Published 19 July 2019 Volume 2019:11 Pages 6727—6739

DOI https://doi.org/10.2147/CMAR.S188746

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Wendi Yan,1,* Xue Wang,1,* Tesi Liu,1 Liyan Chen,2 Longzhe Han,3 Jing Xu,4 Guihua Jin,5 Kenichi Harada,6 Zhenhua Lin,1 Xiangshan Ren1,2

1Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, People’s Republic of China; 2Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, People’s Republic of China; 3Department of Yanbian University Affiliated Hospital, Yanji 133002, People’s Republic of China; 4Department of Shanxi Medical University Medical College, Taiyuan 030001, People’s Republic of China; 5Department of Immunology and Pathogenic Biology, Yanbian University College of Medicine, Yanji 133002, People’s Republic of China; 6Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan

*These authors contributed equally to this work

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.

Keywords: ERO1A, cholangiocarcinoma, survival, prognosis, EMT

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