Liu Qinsong, Xin Lu, Ma Xiaoning, Yuan Yong
Department of Otolaryngology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Heliyon. 2024 Aug 30;10(17):e37219. doi: 10.1016/j.heliyon.2024.e37219. eCollection 2024 Sep 15.
The inhibitor MLN4924 of Neural Precursor Cell-Expressed Developmentally Down-Regulated 8 (NEDD8) Activating Enzyme 1 (NAE1) has been found to suppress the growth of nasopharyngeal carcinoma (NPC). However, its effect on NPC's radiotherapy sensitivity remains unclear.
By integrating single-cell RNA sequencing and bulk RNA sequencing, we predict the impact of NAE1 on the cell cycle, cell death, and its relationship with radiotherapy sensitivity and prognosis in NPC. The effect of inhibiting NAE1 on NPC cell behavior and radiation sensitivity is explored through MLN4924 intervention in vitro and in vivo. We construct a prognosis prediction model based on NAE1 using machine learning methods and validate the efficacy of NAE1 and the model in clinical cohorts.
NPC patients with high NAE1 expression have better prognosis and higher expression in the radiotherapy-sensitive group. Inhibiting NAE1 with MLN4924 causes cell cycle arrest in NPC cells, preventing them from entering the G2/M phase, thereby inhibiting proliferation but not affecting migration and metastasis. However, in vitro and in vivo experiments demonstrate that inhibiting NAE1 with MLN4924 leads to increased resistance of NPC to radiation.
Targeting NAE1 for NPC treatment may have dual effects, inhibiting NPC proliferation while also increasing radiation resistance.
神经前体细胞表达的发育下调基因8（NEDD8）激活酶1（NAE1）的抑制剂MLN4924已被发现可抑制鼻咽癌（NPC）的生长。然而，其对NPC放疗敏感性的影响仍不清楚。
通过整合单细胞RNA测序和批量RNA测序，我们预测NAE1对NPC细胞周期、细胞死亡的影响及其与放疗敏感性和预后的关系。通过MLN4924在体外和体内的干预，探索抑制NAE1对NPC细胞行为和辐射敏感性的影响。我们使用机器学习方法构建基于NAE1的预后预测模型，并在临床队列中验证NAE1和该模型的有效性。
NAE1高表达的NPC患者预后较好，且在放疗敏感组中的表达更高。用MLN4924抑制NAE1会导致NPC细胞周期停滞，阻止其进入G2/M期，从而抑制增殖，但不影响迁移和转移。然而，体外和体内实验表明，用MLN4924抑制NAE1会导致NPC对辐射的抗性增加。
靶向NAE1治疗NPC可能具有双重作用，抑制NPC增殖的同时也增加辐射抗性。
