Lnc-PVT1作为重要的长链非编码RNA分子, 在调控恶性肿瘤放疗抵抗方面具有重要作用，但其作用机制目前尚未完全明确。申请人首次通过RNA pull-down质谱技术发现lnc-PVT1可以与组蛋白乙酰化转移酶KAT7相结合，并促进KAT7正向调控H3K14乙酰化。进一步预试验发现乙酰化的H3K14可能招募更多的TRIM24结合HDGF启动子并上调其表达。提示HDGF可能是lnc-PVT1的一个新的靶基因。因此，本研究将进一步从分子水平探讨lnc-PVT1招募KAT7乙酰化激活HDGF，进而促进三阴乳腺癌放疗抵抗的机制，同时研究lnc-PVT1在三阴乳腺癌放疗抵抗中的预后意义及临床价值。本研究对阐明三阴乳腺癌放疗抵抗的分子机制具有一定的理论意义，同时也为治疗三阴乳腺癌提供新的靶点。

Lnc-PVT1, a critical long non-coding RNA molecular, plays essential roles in radioresistance. However, its mechanisms remain unclear. Using RNA pull-down mass spectrometry method, our preliminary results demonstrate that lnc-PVT1 binds to histone acetyltransferase KAT7 and induces H3K14 acetylation. In addition, H3K14ac recruits more TRIM24 to HDGF promoter and activates HDGF transcription. Therefore, this project intends to uncover: 1) Lnc-PVT1 recruits KAT7 to acetylatedly activate HDGF transcription; 2) The role of lnc-PVT1 in radioresistance of triple-negative breast cancer; 3) The prognostic significance and clinical value of lnc-PVT1 in triple-negative breast cancer. This study will clarify the molecular mechanism of radioresistance in triple-negative breast cancer, and provide a new molecular target for triple-negative breast cancer.