Yan Wendi, Wang Xue, Liu Tesi, Chen Liyan, Han Longzhe, Xu Jing, Jin Guihua, Harada Kenichi, Lin Zhenhua, Ren Xiangshan
Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, People's Republic of China.
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, People's Republic of China.
Cancer Manag Res. 2019 Jul 19;11:6727-6739. doi: 10.2147/CMAR.S188746. eCollection 2019.
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.
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.
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.
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.
内质网氧化还原酶1-α（ERO1A）是一种缺氧诱导的内质网氧化酶，可调节氧化蛋白的翻译和折叠。本研究旨在探讨ERO1A的临床病理意义及其对胆管癌细胞生物学行为的影响。
采用免疫组织化学染色检测胆管癌中ERO1A、癌胚抗原（CEA）和糖类抗原19-9（CA19-9）的表达。进行免疫荧光染色以检测ERO1A在胆管癌细胞中的亚细胞定位。通过蛋白质免疫印迹法验证耗尽或过表达后ERO1A在胆管癌细胞中的表达。然后，通过MTT法和集落形成试验验证ERO1A对胆管癌细胞增殖的影响。进行伤口愈合试验和迁移试验以检测ERO1A对细胞迁移能力的影响。最后，我们探讨了ERO1A在上皮-间质转化和Akt/mTOR信号通路中的作用。
在本研究中，我们的数据表明ERO1A、CEA和CA19-9在胆管癌组织中表达，阳性率分别为95%、95%和55%。ERO1A的高表达与胆管癌的临床分期和病理分期相关。体外数据表明，ERO1A的缺失可抑制胆管癌细胞的增殖和迁移，反之亦然。此外，ERO1A已被证明与上皮-间质转化和Akt/mTOR通路密切相关。
总之，我们发现ERO1A的高表达与患者预后不良相关，ERO1A可促进胆管癌细胞的增殖和迁移。总之，ERO1A可作为预测胆管癌预后的独立生物标志物。
