Abstract：
The expression pattern of MUC1-C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1-C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1-C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co-immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF-κB signaling pathways in the interaction between MUC1-C and hypoxia-inducible factor-1α (HIF-1α) was investigated. MUC1-C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large-volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume-mediated hypoxia resulted in increased expression of MUC1-C and HIF-1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF-κB signaling pathway was weakened, allowing NF-κB to promote the positive feedback formation of MUC1-C and HIF-1α. Simultaneously, EGLN2-mediated degradation of HIF-1α was reduced. This ultimately led to elevated HIF-1α-mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.
摘要：
MUC1-C在肿瘤中的表达模式与肿瘤进展密切相关；然而，其具体机制尚不清楚。免疫组化和Westernblot检测MUC1-C在癌组织和癌旁正常组织中的表达。使用CCK8测定法测定细胞对吉西他滨的IC50。研究了缺氧和MUC1-C对膀胱癌细胞行为和代谢特征的影响。通过蛋白质印迹和聚合酶链反应评估基因表达。通过免疫共沉淀分析基因之间的关系，免疫荧光和蛋白质印迹。最后,研究了EGLN2和NF-κB信号通路在MUC1-C与缺氧诱导因子-1α（HIF-1α）相互作用中的作用。MUC1-C在膀胱癌组织中的表达明显高于癌旁正常组织,特别是在大体积肿瘤中，与肿瘤分级等临床特征密切相关。肿瘤体积介导的缺氧导致膀胱癌细胞中MUC1-C和HIF-1α的表达增加。在缺氧的刺激下，EGLN2对NF-κB信号通路的抑制作用减弱,允许NF-κB促进MUC1-C和HIF-1α的正反馈形成。同时,EGLN2介导的HIF-1α降解减少。这最终导致HIF-1α介导的下游基因表达升高，促进葡萄糖摄取和糖酵解增加，并最终导致化疗耐药性和恶性肿瘤。
