Molecular targeted drug discovery for cancer cell radiosensitization using RNA aptamars

众所周知，阻断与DNA修复机制有关的蛋白激酶，如DNA-PKcs、ATM或ATR，可以增强对电离辐射(IR)的敏感性。从这个角度来看，我们希望通过利用这一机制来提高肿瘤细胞对放射治疗的敏感性。与DNA修复机制相关的蛋白激酶是通过磷酸化来激活的。因此，我们尝试制作RNA工程技术，并将开发新的辐射增敏药物作为治疗癌症的分子靶向药物。在本实验中，我们通过SELEX针对DNA-PKcs的磷酸化位点制作了RNA适配子。在本研究中，我们制备了针对DNA-PKcs磷酸化位点的RNA适配子。此外，还利用下一代测序技术对它们的特异性模板序列进行了分析，并对一些可能特异性识别DNA-PKcs的基因进行了重点分析。将该RNA分子导入U2OS细胞，检测是否能增加对辐射的敏感性。综上所述，我们发现了一些能增强U2OS细胞辐射敏感性的RNA分子。

It is well known that blocking protein kinases related to DNA repair machinery such as DNA-PKcs, ATM, or ATR enhance sensitivity to ionizing radiation (IR). From this point of view, we expect that tumor cell sensitivity against radiotherapy is enhanced by exploiting this mechanism. Protein kinases related to DNA repair machinery are activated by being phosphorylated. Therefore we attempted making the RNA engineering technology, and will develop new radiation sensitization medicine as a molecular target drug for cancer. In this experiment, we are making RNA aptamers against phosphorylated site of DNA-PKcs by SELEX. In this research, we produced RNA aptamers specific to DNA-PKcs phosphorylation site. Furtheremore their specific template sequences were analyzed by next-generation sequencing technology, and some that may recognize DNA-PKcs specifically were focused. U2OS cells are transfected with the RNA molecules, we tested whether can increase sensitivity of radiation. In conclusion, we found some RNA molecules that enhance sensitivity of radiation for U2OS cells.