Abstract: Resistance to radiotherapy is the reason for treatment failure in most patients with colorectal cancer. In this study, bioinformatics methods were used to screen differential genes (DEGs) in cancer tissues after radiotherapy, and to find therapeutic targets related to radiosensitivity. After screening the cells by cell cycle mediator ribonucleotide reductase regulatory subunit M2 (RRM2) expression, the cells were transfected with lipofectamine 2000 and irradiated with 3 Gy. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of RRM2 in colorectal cancer. Cell viability was measured by MTT assay. Flow cytometry was used to determine cell cycle and apoptosis. A total of 4 269 DEGs were identified, and RRM2 was found to be the most significant difference. Compared with intestinal epithelial FHC cells, RRM2 expression level significantly increased in tumor cells (P<0.05). Compared with NC group, RRM2 overexpression promoted cell viability. Compared with the 3 Gy group, RRM2 overexpression could delay the killing effect of radiotherapy on the cells. Compared with NC group, overexpression of RRM2 reduced the apoptosis rate, while inhibition of RRM2 increased the apoptosis rate. The combination of si-RRM2 and irradiation showed better results compared to that with si-RRM2 or irradiation alone. Overexpression of RRM2 caused cell aggregation in S phase, while knockdown of RRM2 caused cell aggregation in G1 phase. In addition, irradiation caused a significant G1 phase arrest, while RRM2 knockdown together with irradiation caused a more significant G1 phase arrest. This suggests that RRM2 mediates cell cycle of CRC cells and affects the radiosensitivity of CRC through cell cycle. This study provides important data support for the development of combined therapy for colorectal cancer.

Key words: RRM2; colorectal cancer; cell cycle; radiosensitivity; therapeutic target

（Acta Laser Biology Sinica, 2024, 33(1): 065-072）