PDF(Pubmed)
Abstract：
Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both in vitro and in vivo. ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.
摘要：
化疗耐药是改善胰腺癌（PC）预后的障碍。然而,ISG15在PC中的生物学功能及其是否与化疗耐药相关尚不清楚。这里,我们旨在揭示ISG15在PC中的临床意义及其在癌症进展和治疗抵抗中的调节机制。ISG15是一种参与翻译后修饰的蛋白质，在PC组织中升高。临床上,较高的ISG15表达与较高的PC等级相关，对治疗的抵抗力更强，预后较差。此外，ISG15促进了扩散，迁移,入侵,PC细胞的集落形成和对吉西他滨的抗性，一种经典的PC化疗药物，在体外和体内。ISG15通过与ATG7结合，减少其降解，促进PC细胞的进展和对治疗的抵抗，从而导致PC细胞自噬增强。在PC干预期间,ISG15可用作化疗剂如吉西他滨的潜在诊断标记和敏化剂。
