Department of Otolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Sleep Medicine Centre, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Sci Rep. 2024 Oct 15;14(1):24140. doi: 10.1038/s41598-024-73239-5.
Nasopharyngeal carcinoma (NPC) presents a significant medical challenge due to its high incidence rate and poor prognosis, which are attributed primarily to tumor metastasis and drug resistance. Sine oculis homeobox homolog 1 (SIX1) has been identified as a crucial target for cancer treatment. However, its role in NPC remains incompletely understood. This study investigated the mechanisms by which the degradation of the SIX1 protein, which is mediated by ubiquitin, affects the malignant characteristics of NPC throughout the cell cycle. Our findings reveal that reduced expression of the itchy E3 ubiquitin ligase E3 (ITCH) in NPC impedes the degradation of the SIX1 protein, leading to enhance oncogenic properties. Knockdown experiments which SIX1 was inhibited demonstrated a decrease in the proliferation, migration, and invasion of NPC cell lines, whereas overexpression of SIX1 yielded the opposite effects. Further experimental validation revealed that SIX1 promotes NPC progression via the cell division cycle 27 (CDC27)/cyclin B1 axis. These findings provide valuable insights into potential therapeutic targets and prognostic indicators for NPC treatment, emphasizing the ITCH/SIX1/CDC27/cyclin B1 axis as a promising target for novel therapies.
鼻咽癌（NPC）由于其高发病率和预后不良，是一个重大的医学挑战，主要归因于肿瘤转移和耐药性。Sine oculis homeobox homolog 1（SIX1）已被确定为癌症治疗的重要靶点。然而，其在 NPC 中的作用仍不完全清楚。本研究探讨了泛素介导的 SIX1 蛋白降解如何通过细胞周期影响 NPC 的恶性特征。我们的研究结果表明，NPC 中瘙痒 E3 泛素连接酶 E3（ITCH）表达降低会阻碍 SIX1 蛋白的降解，从而增强致癌特性。抑制 SIX1 的敲低实验表明，NPC 细胞系的增殖、迁移和侵袭减少，而 SIX1 的过表达则产生相反的效果。进一步的实验验证表明，SIX1 通过细胞分裂周期 27（CDC27）/细胞周期蛋白 B1 轴促进 NPC 的进展。这些发现为 NPC 治疗提供了有价值的治疗靶点和预后指标，强调了 ITCH/SIX1/CDC27/细胞周期蛋白 B1 轴作为新型治疗方法的有前途的靶点。
