背景:宫颈癌(CC)与女性的高发病率和高死亡率有关。受体相互作用蛋白激酶(RIPK)家族的成员是炎症和细胞死亡的重要调节因子。然而,的特点,分子功能,RIPK1在CC中的表达机制尚不清楚。
方法:为了确定RIPK1是否可以用于CC的靶向治疗,我们评估了临床重要性,生物学功能,以及RIPK1在50例CC患者中的潜在影响。我们利用免疫组织化学染色,转染,西方印迹,细胞计数试剂盒-8测定,集落形成试验,和伤口愈合试验等,阐明RIPK1在CC中的作用。
结果:RIPK1在肿瘤组织中的表达高于癌旁组织。CC的不良预后与RIPK1上调有关。此外,沉默RIPK1显著抑制增殖,迁移,和CC细胞的体外侵袭。我们还确定RIPK1增加细胞迁移,入侵,通过调节核因子κB(NF-κB)和肿瘤坏死因子(TNF)进行增殖。
结论:RIPK1激活NF-κB并调节TNF释放,以增强CC细胞的增殖和扩散,同时抑制其凋亡。因此,RIPK1在CC的形成和发展中起关键作用,是CC治疗的潜在靶标。
BACKGROUND: Cervical cancer (CC) is associated with high morbidity and mortality rates in women. Members of the receptor-interacting protein kinase (RIPK) family are important regulators of inflammation and cell death. However, the characteristics, molecular functions, and expression mechanisms of RIPK1 in CC remain unclear.
METHODS: To determine whether RIPK1 can be used for targeted therapy of CC, we assessed the clinical importance, biological function, and potential impact of RIPK1 in CC in 50 patients with CC. We utilized immunohistochemical staining, transfection, western blotting, cell counting kit-8 assay, colony formation assay, and wound healing assays among others, to elucidate the role of RIPK1 in CC.
RESULTS: RIPK1 expression was higher in tumor tissues than in paracancerous tissues. Poor prognosis of CC was linked to RIPK1 upregulation. Furthermore, silencing RIPK1 significantly inhibited the proliferation, migration, and invasion of CC cells in vitro. We also established that RIPK1 increased cell migration, invasion, and multiplication by regulating nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF).
CONCLUSIONS: RIPK1 activates NF-κB and regulates TNF release to enhance the proliferation and spread of CC cells while suppressing their apoptosis. Therefore, RIPK1 plays a key role in the formation and progression of CC and is a potential target for CC treatment.