局部进展期直肠癌（LARC）术前新辅助放化疗（neoCRT）后的肿瘤退缩分级（TRG）与其内在的放射敏感性相关，AJCC-TRG0即病理完全缓解（pCR）患者预后最好，但调控直肠癌放射敏感性的分子机制尚不明了。我们前期研究已对10例LARC直肠癌（4例pCR，6例非pCR）neoCRT前癌组织进行RNA提取、mRNA转录组二代测序及通过生物信息学分析，发现UBE2W在pCR组高表达，而在非pCR组低表达或无表达，二组差异显著。已知泛素结合酶E2W（UBE2W）与多个参与DNA损伤反应（DDR）的泛素连接酶发生相互作用。本项目将通过体内外实验，研究UBE2W介导直肠癌放射敏感性的相关信号通路，筛查与DDR 相关的泛素连接酶，并进一步研究与UBE2W相互作用的泛素连接酶及其功能，从而揭示UBE2W调控直肠癌放射敏感性的分子机制。本研究为深入开展增强直肠癌放射敏感性的相关研究提供新的分子靶点。

Tumor regression grade (TRG) of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (neoCRT) correlated significantly with patient’s prognosis. Patients with AJCC-TRG0 (pathological complete response, pCR) have the best survival outcomes. But the mechanism mediating the radiosensitivity of rectal cancer is still unclear. Our research team has collected fresh tumor tissues from 10 rectal cancer patients (4 pCR, 6 non-pCR) before they received neoCRT, performed mRNA next-generation sequencing and bioinformatics analysis. We found expression of Ubiquitin-Conjugating Enzyme E2W (UBE2W) was high in pCR group and low or negative in non-pCR group. Recent literature showed UBE2W could interact with multiple ubiquitin ligases involved in DNA damage response (DDR). The current project will investigate UBE2W-mediated signaling pathways in radiosensitivity of rectal cancer with in vitro and in vivo experiments, screen ubiquitin ligases involved in DDR and also interact with UBE2W, in order to reveal the mechanism of regulating radiosensitivity of rectal cancer by UBE2W. This project will provide potential target for radiosensitization in the treatment of rectal cancer.