lncRNA-29314916-CCNB2通路在重离子放疗中的辐射增敏机理研究

提高重离子束单位剂量对肿瘤细胞的杀伤率，是改善肿瘤放疗疗效的关键之一。lncRNAs以其多样的调控模式正成为放射治疗领域的研究热点。我们研究发现，lncRNAs在直肠癌细胞经辐射后具有特征性的表达谱；临床表型关联分析显示，lncRNA-29314916与直肠癌临床预后密切相关；共表达网络及质谱的初步结果显示：lncRNA-29314916与蛋白CCNB2可特异性结合。我们推测：重离子辐射-lncRNA-29314916-CCNB2通路在放疗引发直肠癌细胞死亡过程中具有重要功能。我们拟进一步通过质谱、RNA免疫共沉淀及染色质免疫共沉淀等手段，在细胞及动物水平深入研究相关机制，揭示lncRNA-29314916在重离子等辐射诱发直肠癌死亡过程中所发挥的重要功能。本研究有助于我们系统性理解lncRNAs在放疗过程中的作用机制，为临床进一步的应用研究提供潜在的诊断及治疗靶点。

Improve the killing rate of heavy ion for tumor cells is one of the key fields to rectum carcinoma radiotherapy. Giving the diverse regulated-modes, the long non-coding RNA (lncRNAs) is becoming one of the hot research fields of cancer radiotherapy. In our previous studies, lncRNAs have a characteristic expression profiling of rectum carcinoma after heavy ion radiation; association analysis revealed that higher levels of lncRNA-29314916 correlated with higher overall survival of patients; lncRNA-mRNA co-expression network and mass spectrum also found the binding specificity for lncRNA-29314916 and CCNB2 protein. Then, we hypotheses that the heavy ion radiation-lncRNA-29314916-CCNB2 axis may have important roles in rectum carcinoma radiotherapy. Therefore, we intend to use the mass spectrum, RNA pulldown, RIP and CHIP methods to study the roles of lncRNA-29314916 at the cellular and animal level after heavy ion radiation. This study can help us to systematically understand the mechanism of lncRNAs in rectum carcinoma, and to provide potential diagnostic and therapeutic targets for clinical cancer research.