Department of Pediatrics, The First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang , Liaoning, 110001 China.
Department of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang , Liaoning, 110001 China.
Int J Med Sci. 2021 Jul 25;18(14):3342-3352. doi: 10.7150/ijms.62870. eCollection 2021.
: Incidence and mortality rates of breast cancer are increasing in women worldwide. Immunotherapy is a relatively popular treatment modality for all malignant tumors including breast cancer in recent years. Interferon γ-inducible protein 30 (IFI30) could catalyze the reduction of disulfide bonds and enhance major histocompatibility complex (MHC) class II-restricted antigen processing. Recent studies showed that IFI30 played an important role in the immune response of malignant tumors. : The Cancer Genome Atlas (TCGA) database and clinical proteomic tumor Analysis consortium (CPTAC) database were applied to predict the role of IFI30 in breast cancer and the relationship between IFI30 and prognosis of breast cancer patients. Then we detected the expression of IFI30 in clinical samples of breast cancer patients, and analyzed the relationship between IFI30 and the prognosis of breast cancer patients. We used lentivirus infection method to construct a stable IFI30 knockdown cell line, and detected the effect of IFI30 in breast cancer cells. Nude mice tumor bearing experiment was performed to investigate the effect of IFI30 on breast cancer cells . Western blot was used to verify the regulation of autophagy related protein LC3 and p62 by IFI30. We found that IFI30 was highly expressed in breast cancer tissues and was associated with poor outcome of patients. The knockdown of IFI30 could inhibit the proliferation, migration and invasion of breast cancer cells and significantly inhibit tumor growth . Increased accumulation of LC3-II and p62 suggested impaired autophagy in IFI30 knockdown cells. As a result, we suggested that IFI30 might play a key role in the initiation and progression of human breast cancer and might be a new therapeutic target in breast cancer.
乳腺癌的发病率和死亡率在全球范围内呈上升趋势。免疫疗法是近年来治疗包括乳腺癌在内的所有恶性肿瘤的一种相对流行的治疗方式。干扰素 γ 诱导蛋白 30（IFI30）可以催化二硫键的还原，并增强主要组织相容性复合体（MHC）II 类限制的抗原加工。最近的研究表明，IFI30 在恶性肿瘤的免疫反应中发挥重要作用。
我们应用癌症基因组图谱（TCGA）数据库和临床蛋白质组肿瘤分析联盟（CPTAC）数据库来预测 IFI30 在乳腺癌中的作用及其与乳腺癌患者预后的关系。然后，我们检测了乳腺癌患者临床样本中 IFI30 的表达，并分析了 IFI30 与乳腺癌患者预后的关系。我们使用慢病毒感染方法构建了稳定的 IFI30 敲低细胞系，并检测了 IFI30 对乳腺癌细胞的影响。进行裸鼠肿瘤荷瘤实验以研究 IFI30 对乳腺癌细胞的影响。Western blot 用于验证 IFI30 对自噬相关蛋白 LC3 和 p62 的调节。
我们发现 IFI30 在乳腺癌组织中高表达，与患者的不良预后相关。IFI30 的敲低可抑制乳腺癌细胞的增殖、迁移和侵袭，并显著抑制肿瘤生长。LC3-II 和 p62 的积累增加表明 IFI30 敲低细胞中的自噬受损。
因此，我们认为 IFI30 可能在人类乳腺癌的发生和发展中发挥关键作用，可能成为乳腺癌的新治疗靶点。
