HDAC7激活非经典NF-κB通路促进鼻咽癌恶性进展的功能和机制研究

组蛋白去乙酰化酶（HDACs）是肿瘤治疗的理想靶点，但其在鼻咽癌(NPC)中的作用和机制不明，临床应用价值仍待揭示。申请人已证实HDAC7在NPC中高表达且促进NPC进展，是NPC预后不良的独立危险因子，表明HDAC7是NPC治疗的潜在靶点，但其促瘤机制仍待揭示。前期研究结果初步证实HDAC7与NFKB2互作，抑制NFKB2的赖氨酸乙酰化水平，促进其向p52转化活化，提示存在“HDAC7介导NFKB2的去乙酰化，促进其活性转化而激活非经典NF-κB通路，促进NPC进展”的新机制。因此本项目拟开展相关研究揭示HDAC7调控NFKB2乙酰化修饰的机制和意义，阐明NFKB2乙酰化在非经典NF-κB通路活化和NPC恶性进展中的作用，明确HDAC7/非经典NF-κB通路活化的临床价值。项目的成功实施，将为靶向抑制HDAC7/非经典NF-κB通路治疗NPC的新思路提供科学依据，理论和临床应用价值兼具。

Histone deacetylases (HDACs) are ideal targets for tumor therapy. However, due to the lack of researches on the role and mechanism of HDACs in nasopharyngeal carcinoma(NPC), its clinical application value in NPC remains to be revealed. Applicant have confirmed that HDAC7 upregulation plays a tumor-promoting function in NPC and is an independent risk factor for poor prognosis of patients with NPC, indicating that HDAC7 is a potential target for the treatment of NPC. However, the mechanism of HDAC7’s tumor-promoting functions in NPC remains to be revealed. The results of previous studies confirmed that HDAC7 could interact with NFKB2, negatively regulate its acetylation level and promote its conversion to p52, suggesting a new mechanism that “HDAC7 mediates the deacetylation of NFKB2, promotes its activity conversion, subsequently activates the non-canonical NF-κB pathway, and eventually promotes NPC progression.” This project intends to carry out related researches to reveal the mechanism and clinical significance of HDAC7 regulating NFKB2 acetylation, to clarify the role of NFKB2 acetylation in the activation of non-classical NF-κB pathway and the malignant progression of NPC, and find out the clinical values of activation of HDAC7/non-classical NF-κB pathway. The successful implementation of the project will provide a scientific basis for new ideas for the inhibition of HDAC7/non-classical NF-κB pathway in the treatment of NPC, and it will have both theoretical and clinical application value.