Cancer Institute, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), No. 519, Kunzhou Road, Kunming, 650118, China.
Department of Medical Oncology II, The Third People's Hospital of Honghe Prefecture, Gejiu, Honghe, China.
J Mol Histol. 2023 Dec;54(6):621-631. doi: 10.1007/s10735-023-10149-2. Epub 2023 Sep 30.
Endoplasmic reticulum oxidoreductin 1α (ERO1α) is an oxidase that exists in the endoplasmic reticulum and plays an important role in regulating oxidized protein folding and tumor malignant progression. However, the specific role and mechanism of ERO1α in the progression of colorectal cancer (CRC) have not yet been fully elucidated. In this study, 280 specimens of CRC tissues and adjacent noncancerous tissues were collected to detect the expression of ERO1α and analyze the clinical significance. ERO1α was stably knocked-down in RKO and HT29 CRC cells to investigate its function and mechanism in vitro and in vivo. We found that ERO1α was remarkably upregulated in CRC tissues and high ERO1α expression is associated with N stage and poor prognosis of CRC patients. ERO1α knockdown in CRC cells significantly inhibited the proliferation and induced apoptosis while inactivating the PI3K/AKT pathway. Rescue assays revealed that AKT activator 740Y-P could reverse the effects on proliferation and apoptosis of ERO1α knockdown in CRC cells. In vivo tumorigenicity assay also confirmed that ERO1α knockdown suppressed tumor growth. Taken together, our findings demonstrated ERO1α promotes the proliferation and inhibits apoptosis of CRC cells by regulating the PI3K/AKT pathway. High expression of ERO1α is associated with poor prognosis in CRC patients, and ERO1α could be a potential therapeutic target for CRC.
内质网氧化还原酶 1α（ERO1α）是一种存在于内质网中的氧化酶，在调节氧化蛋白折叠和肿瘤恶性进展中发挥重要作用。然而，ERO1α在结直肠癌（CRC）进展中的具体作用和机制尚未完全阐明。在本研究中，收集了 280 例 CRC 组织和相邻非癌组织标本，检测 ERO1α的表达，并分析其临床意义。在 RKO 和 HT29 CRC 细胞中稳定敲低 ERO1α，以在体外和体内研究其功能和机制。我们发现 ERO1α在 CRC 组织中显著上调，高 ERO1α表达与 CRC 患者的 N 分期和预后不良相关。在 CRC 细胞中敲低 ERO1α显著抑制增殖并诱导细胞凋亡，同时使 PI3K/AKT 通路失活。挽救实验表明，AKT 激活剂 740Y-P 可逆转 ERO1α 敲低对 CRC 细胞增殖和凋亡的影响。体内肿瘤发生实验也证实了 ERO1α 敲低抑制了肿瘤生长。综上所述，我们的研究结果表明，ERO1α 通过调节 PI3K/AKT 通路促进 CRC 细胞的增殖并抑制细胞凋亡。高表达 ERO1α与 CRC 患者预后不良相关，ERO1α 可能成为 CRC 的潜在治疗靶点。
