Wei Jing, Jiang Jinxiang, Zhang Shuhong, Dong Shuai
Department of Gynaecology and Obstetrics, The 960th Hospital of the Joint Logistics Support Force of the People`s Liberation Army of China, Jinan, China.
Department of Outpatient Laboratory, Qingdao Municipal Hospital, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
Cytojournal. 2024 Nov 22;21:49. doi: 10.25259/Cytojournal_81_2024. eCollection 2024.
Endometrial cancer (EC) is a common gynecological malignancy, and its metastasis is one of the primary causes of treatment failure. Immunoglobulin superfamily member 1 (IGSF1), a membrane protein, has been associated with the aggressiveness and metastatic capability of various cancers. However, the role and mechanism of this protein in EC remains unclear. Therefore, this study aimed to explore the role of IGSF1 in EC and its possible mechanism.
In this study, IGSF1 expression was knocked down through small interfering RNA and short hairpin RNA techniques, and its levels were controlled through overexpression experiments to observe its effects on Ishikawa cells. Wound healing assays, Transwell migration and invasion assays, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence double labeling were performed to evaluate the ability of cells to migrate, invade, and express markers of the epithelium mesenchymal transition (EMT). In addition, we investigated the regulatory role of IGSF1 in Myc proto-oncogene (c-Myc) expression and its function in lung metastasis through animal models of lung metastasis.
The results indicate that IGSF1 knockdown inhibited EMT and greatly reduced the invasion ability of Ishikawa cells ( < 0.01). Animal experiments demonstrated that IGSF1 knockdown reduced the number of pulmonary metastatic foci ( < 0.001). On the other hand, IGSF1 overexpression increased Ishikawa cells' ability to migrate and invade ( < 0.01). IGSF1 overexpression also inhibited E-cadherin expression and promoted that of vimentin ( < 0.001). The expression of c-Myc decreased following IGSF1 knockdown and increased after its overexpression. Silencing of c-Myc reversed the oncogenic effects of IGSF1 ( < 0.01).
IGSF1 promotes EMT and metastasis in EC through the upregulation of the c-Myc expression. IGSF1 may serve as a potential therapeutic target for EC, and its inhibition can offer new strategies for mitigating the aggressiveness and metastatic potential of this malignancy.
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，其转移是治疗失败的主要原因之一。免疫球蛋白超家族成员1（IGSF1）是一种膜蛋白，与多种癌症的侵袭性和转移能力有关。然而，该蛋白在EC中的作用和机制仍不清楚。因此，本研究旨在探讨IGSF1在EC中的作用及其可能的机制。
在本研究中，通过小干扰RNA和短发夹RNA技术敲低IGSF1表达，并通过过表达实验控制其水平，以观察其对Ishikawa细胞的影响。进行伤口愈合试验、Transwell迁移和侵袭试验、定量实时聚合酶链反应、蛋白质免疫印迹法和免疫荧光双标记，以评估细胞迁移、侵袭和表达上皮间质转化（EMT）标志物的能力。此外，我们通过肺转移动物模型研究了IGSF1对Myc原癌基因（c-Myc）表达的调节作用及其在肺转移中的功能。
结果表明，敲低IGSF1可抑制EMT，并显著降低Ishikawa细胞的侵袭能力（<0.01）。动物实验表明，敲低IGSF1可减少肺转移灶的数量（<0.001）。另一方面，IGSF1过表达增加了Ishikawa细胞的迁移和侵袭能力（<0.01）。IGSF1过表达还抑制了E-钙黏蛋白的表达，并促进了波形蛋白的表达（<0.001）。敲低IGSF1后c-Myc的表达降低，过表达后c-Myc的表达增加。沉默c-Myc可逆转IGSF1的致癌作用（<0.01）。
IGSF1通过上调c-Myc表达促进EC中的EMT和转移。IGSF1可能是EC的潜在治疗靶点，抑制它可为减轻这种恶性肿瘤的侵袭性和转移潜能提供新策略。
