术前放射治疗是局限性晚期结直肠癌的常规治疗手段，结直肠癌放射抵抗性研究具有重要的临床价值。LncRNA作为一类新的功能分子，代表新的方向领域。我们前期研究发现敲低lnc-RI（本实验室筛选获得的放射诱导表达lncRNA）水平，抑制LIG4（NHEJ修复关键分子）表达的同时增加DNA双链断裂，降低细胞的放射抵抗性。进一步研究发现，lnc-RI在部分结直肠癌标本呈现高表达。结合DSB修复水平是影响细胞放射抗性关键因素的文献报道，提出如下科学设想： lnc-RI通过正调控LIG4，促进结直肠癌细胞DSBs的NHEJ修复，增强其放射抵抗性。拟开展三个方面研究：1）证实lnc-RI通过促进DSB的NHEJ修复增强结直肠癌细胞放射抵抗性；2）明确LIG4在lnc-RI调节放射抵抗性中的作用及lnc-RI调节LIG4的机制；3）结合临床肿瘤病例分析lnc-RI表达水平与结直肠癌放射抵抗性的相关性。

Colorectal cancer preoperative radiotherapy is a routine treatment of advanced colorectal cancer. Research on colorectal cancer radiation resistance prediction and intervention is an important. Lnc-RI is a long non-coding RNA induced by radiation, which was previously identified by the applicant. Previous studies have shown that lnc-RI may regulate the NHEJ repair process of DNA double-strand breaks by modulating the expression of LIG4. Further study showed that lnc-RI showed high expression in some colorectal cancer specimens and found that colorectal cancer cell line HCT-116 lnc-RI high expression levels had higher radiation resistance than lnc-RI low expression cells. It is hypothesized that the high expression of lnc-RI enhances its radiation resistance by positively regulating LIG4 and promoting NHEJ repair of DSBs in postoperative colorectal cancer cells. Three studies were conducted: 1) confirmed that lnc-RI enhanced the radiosensitivity of colorectal cancer cells by promoting DSB NHEJ repair; 2) clarified the role of LIG4 in lnc-RI regulation of radiation resistance and lnc-RI regulation of LIG4； 3) combined with clinical tumor case analysis the correlation between lnc-RI expression levels and colorectal cancer radiation resistance.