Abstract：
Triple-negative breast cancer (TNBC) is recognized as the most malicious form of breast cancer and exhibits an alarming tendency for recurrence, a heightened propensity for metastasis, and an overwhelmingly grim prognosis. Therefore, effective therapy approaches for TNBC are urgently required. In this study, the interferon-stimulated gene 15 (ISG15) expression level was analyzed by bioinformatics and verified by Western blot analysis. The effects of ISG15 on the proliferation and metastasis of TNBC cells were assessed using MTT, Colony formation, EdU, Transwell, and Flow cytometry assays. We also developed a cancer cell-biomimetic nanoparticle delivery system and evaluated its therapeutic efficacy in vivo. In this study, we reported that ISG15 was upregulated in TNBC, and its high expression level correlated with an increased risk of tumorigenesis. Through in vitro and in vivo studies, we discovered that ISG15 knockdown drastically suppressed cell proliferation, invasion, and migration and induced apoptosis in TNBC cells. Our findings revealed that ISG15 was a candidate therapeutic target in TNBC because of its key role in malignant growth and invasion. Moreover, co-immunoprecipitation showed that ISG15 exerted oncogenic functions through its interaction with ATP binding cassette subfamily E member 1 and activated the Janus kinase/signal transducers and activators of the transcription signaling pathway. Furthermore, we created a nanoparticle-based siRNA camouflaged using a cancer cell membrane vesicle delivery system (the CM@NP complex) and confirmed its therapeutic effects in vivo. Our findings confirmed that ISG15 may play a pivotal oncogenic role in the development of TNBC and that CM@siRNA-NP complexes are an effective delivery system and a novel biological strategy for treating TNBC.
摘要：
三阴性乳腺癌（TNBC）被认为是最恶性的乳腺癌形式，并表现出令人担忧的复发趋势，转移倾向加剧，和极其严峻的预后。因此,迫切需要TNBC的有效治疗方法。在这项研究中,通过生物信息学分析干扰素刺激基因15(ISG15)的表达水平,并通过Westernblot分析进行验证.用MTT法评价ISG15对TNBC细胞增殖和转移的影响,殖民地的形成,EdU,Transwell,和流式细胞术测定。我们还开发了一种癌细胞-仿生纳米颗粒递送系统，并评估了其体内治疗效果。在这项研究中,我们报道了ISG15在TNBC中上调，其高表达水平与肿瘤发生风险增加相关。通过体外和体内研究，我们发现ISG15基因敲除可以显著抑制细胞增殖,入侵,和迁移和诱导TNBC细胞凋亡。我们的发现表明，ISG15是TNBC的候选治疗靶标，因为它在恶性生长和侵袭中起着关键作用。此外，免疫共沉淀表明，ISG15通过与ATP结合盒亚家族E成员1的相互作用发挥致癌功能，并激活了Janus激酶/信号转导和转录信号通路的激活剂。此外，我们使用癌细胞膜囊泡递送系统(CM@NP复合物)创建了一种基于纳米颗粒的siRNA伪装,并证实了其在体内的治疗效果.我们的研究结果证实，ISG15可能在TNBC的发展中起着关键的致癌作用，并且CM@siRNA-NP复合物是治疗TNBC的有效递送系统和新的生物学策略。
