肺癌是人类最常见的恶性肿瘤之一。文献报道组蛋白乙酰转移酶MYST2在DNA损伤修复方面发挥重要作用，但其参与肺癌放疗抵抗的机制目前尚未报道。本研究预试验发现MYST2可与LncRNA-PVT1结合形成复合体，促进非小细胞肺癌细胞增殖和放疗抵抗。前期结果初步表明MYST2可以促进H3K14乙酰化，从而募集TIF1并形成复合体，该复合体可与HMG1L2启动子结合，调控HMG1L2的表达，促进NSCLC放疗抵抗。因此，我们推测：MYST2通过和LncRNA-PVT1结合促进H3K14乙酰化，募集TIF1形成蛋白复合体，调控HMG1L2启动子促进HMG1L2转录，进而促进NSCLC的放疗抵抗。本研究将进一步阐明MYST2和LncRNA-PVT1形成复合体正向调控H3K14/TIF1/HMG1L2信号通路的机制，为NSCLC放射治疗增敏提供新的分子靶点，具有重要的理论价值与临床意义。

Lung cancer is one of the most common malignant tumors in human. It has been reported that MYST2 play an important role in DNA damage and repair. However, whether and how MYST2 regulate radioresistance of non-small cell lung cancer (NSCLC) cells remains unknown. Our preliminary data shows that MYST2 can bind to PVT1 and promote lung cancer cell proliferation and radioresistance. We found that MYST2 can bind to PVT1 and the complex of MYST2 and PVT1 is a regulatory of H3K14 acetylation and TIF1. H3K14ac recruits more TIF1 to HMG1L2 promoter and activates HMG1L2 transcription, which promote radioresistance in NSCLC. We propose that MYST2 can bind to PVT1, which leads to increased H3K14 acetylation level, ultimately increase radioresistance of NSCLC cells by promoting the H3K14/TIF1/HMG1L2 signaling pathway. Therefore, this project intends to uncover the mechanism of how the complex of MYST2 and PVT1 positively controls the H3K14/TIF1/HMG1L2 pathway, and explore the role of complex of MYST2 and PVT1 in radioresistance of NSCLC. This study will provide a novel molecular target for radiosensitization of non-small cell lung cancer.