Chen Jingjing, Wang Yilong, Zhao Na, Song Jie, Feng Yongjun
The Li Huili Hospital of Ningbo Medical Cencer, Ningbo, Zhejiang, China.
Department of Otolaryngology, Head & Neck Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Radiat Res. 2025 Aug 1;204(2):143-153. doi: 10.1667/RADE-24-00130.1.
Radiation therapy is one of the most critical methods for the comprehensive treatment of nasopharyngeal carcinoma (NPC). However, radiation resistance limits the effectiveness of radiotherapy. MicroRNAs (miRNAs) are associated with the radiosensitivity of NPC, but their impacts and mechanisms of action require further investigation. Aberrantly expressed miRNAs were screened in NPC and normal tissue. A series of gain-of-function and loss-of-function experiments were conducted to evaluate the biological behavior of miR-144-3p in NPC cells. The role of miR-144-3p in the proliferation and apoptosis of NPC cells was studied. Downstream mechanisms of miR-144-3p were explored through bioinformatics analysis and RNA sequencing, confirmed by dual-luciferase reporter gene assays. We observed downregulation of miR-144-3p in NPC tissue and radiation-resistant cells. Furthermore, upregulation of miR-144-3p in radiation-resistant cells suppressed the enhancement of radiosensitivity in NPC cells. Conversely, inhibiting miR-144-3p decreased radiosensitivity. We also found that miR-144-3p directly targets nuclear factor erythroid 2-related factor 2 (NFE2L2) and inhibits its expression. The results of this study indicate that the miR-144-3p/Nrf2 pathway contributes to reducing the radioresistance of NPC, making it a potential therapeutic target.
放射治疗是鼻咽癌(NPC)综合治疗中最关键的方法之一。然而,放射抗性限制了放射治疗的效果。微小RNA(miRNA)与NPC的放射敏感性相关,但其影响和作用机制仍需进一步研究。在NPC组织和正常组织中筛选异常表达的miRNA。进行了一系列功能获得和功能丧失实验,以评估miR-144-3p在NPC细胞中的生物学行为。研究了miR-144-3p在NPC细胞增殖和凋亡中的作用。通过生物信息学分析和RNA测序探索miR-144-3p的下游机制,并通过双荧光素酶报告基因测定进行验证。我们观察到NPC组织和放射抗性细胞中miR-144-3p的下调。此外,放射抗性细胞中miR-144-3p的上调抑制了NPC细胞放射敏感性的增强。相反,抑制miR-144-3p会降低放射敏感性。我们还发现miR-144-3p直接靶向核因子红细胞2相关因子2(NFE2L2)并抑制其表达。本研究结果表明,miR-144-3p/Nrf2通路有助于降低NPC的放射抗性,使其成为一个潜在的治疗靶点。