Department of Thoracic Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Mol Carcinog. 2022 Oct;61(10):897-909. doi: 10.1002/mc.23441. Epub 2022 Jul 4.
This study aimed to explore the role and underlying mechanism of action of Endoplasmic reticulum oxidoreductin-1 L (ERO1L) in lung adenocarcinoma (LUAD).
The Gene expression profiling interactive analysis database was used to analyze the expression of ERO1L in LUAD cases. The expression of ERO1L and Wnt2 in LUAD tissue was evaluated using immunohistochemistry. We also used western blotting to assess the expression of ERO1L or Wnt2 and the phosphorylation of β-catenin in LUAD cell lines. Plasmid transfection and small interfering RNA were used for overexpression and knockdown of ERO1L in LUAD cells, respectively. The proliferation, invasion and migration of LUAD cells were analyzed using cell viability, Transwell invasion and wound healing assays. The growth of LUAD tumors in animal models was assessed using tumor xenograft experiments.
This study revealed that elevated ERO1L expression was associated with a poor prognosis in LUAD patients. In addition, ERO1L expression was significantly associated with lymph-node metastasis, TNM stage and tumor size. The expression of Wnt2 was positively associated with ERO1L expression in LUAD tissue samples and cell lines. ERO1L overexpression upregulated the expression of Wnt2 and β-catenin phosphorylation in vitro. Additionally, ERO1L was essential for the ubiquitination of Wnt2. Last, ERO1L promoted the proliferation and metastasis of LUAD via the Wnt2 signaling pathway in vitro and in vivo.
These findings suggest that ERO1L was highly expressed in LUAD tissue, and it promoted the proliferation and metastasis of LUAD by activating the Wnt2/β-catenin signaling pathway.
本研究旨在探讨内质网氧化还原酶 1L（ERO1L）在肺腺癌（LUAD）中的作用及其作用机制。
利用基因表达谱交互分析数据库分析 LUAD 病例中 ERO1L 的表达。采用免疫组织化学法评估 LUAD 组织中 ERO1L 和 Wnt2 的表达。我们还使用 Western blot 法评估 LUAD 细胞系中 ERO1L 或 Wnt2 的表达以及β-catenin 的磷酸化。质粒转染和小干扰 RNA 分别用于 LUAD 细胞中 ERO1L 的过表达和敲低。利用细胞活力测定、Transwell 侵袭和划痕愈合试验分析 LUAD 细胞的增殖、侵袭和迁移。利用肿瘤异种移植实验评估 LUAD 动物模型中的肿瘤生长情况。
本研究表明，ERO1L 表达升高与 LUAD 患者的不良预后相关。此外，ERO1L 表达与淋巴结转移、TNM 分期和肿瘤大小显著相关。Wnt2 的表达与 LUAD 组织样本和细胞系中的 ERO1L 表达呈正相关。ERO1L 过表达可上调体外 Wnt2 和β-catenin 磷酸化的表达。此外，ERO1L 是 Wnt2 泛素化所必需的。最后，ERO1L 通过体外和体内的 Wnt2 信号通路促进 LUAD 的增殖和转移。
这些发现表明，ERO1L 在 LUAD 组织中高表达，通过激活 Wnt2/β-catenin 信号通路促进 LUAD 的增殖和转移。
