IRF1 adenovirus

Radiotherapy is one of the main methods for preoperative or postoperative treatment of colorectal cancer (CRC). However, radiotolerance in CRC patients is often a major problem. Interferon regulatory factor 1 (IRF1) is a member of the IRF family and is involved in the development of a variety of diseases, including tumors. Here, researchers explored the role of IRF1 in CRC development and radiosensitivity. The results showed that the expression level of IRF1 in CRC tissues was significantly lower than that in adjacent tissues. IRF1 upregulation inhibited cell proliferation and clone formation, led to G1 phase cell arrest, promoted cell apoptosis, and enhanced the sensitivity of CRC cells to X-ray irradiation. The role of IRF1 in promoting CRC radiosensitivity was further confirmed in a CRC xenograft nude mouse model. In addition, RNA sequencing showed that overexpression of IRF1 in CRC cells significantly increased the expression levels of interferon-induced protein family members interferon α inducible protein 6, interferon-induced transmembrane protein 1, and interferon-induced protein 35. In summary, these studies suggest that upregulation of IRF1 may inhibit the progression of CRC and promote the radiosensitivity of CRC by regulating interferon-induced proteins.

To investigate the effect of IRF1 on CRC growth in vivo, the researchers inoculated CCL244 cells infected with Ad-NC or Ad-IRF1, or transfected with shRNA-NC or shRNA-IRF1 plasmids into nude mice. The results showed that nude mice inoculated with CCL244 cells infected with IRF1 overexpressing adenovirus had a slower tumor formation rate than the Ad-NC infected control group. In contrast, after IRF1 knockdown, the tumor growth rate was significantly faster than that of the other groups (Figure 1A). The tumor volume in the IRF1 upregulation group was the smallest, and the tumor volume in the IRF1 downregulation group was the largest (Figure 1A). Observation of whole liver specimens revealed that the number of liver metastases in the IRF1 upregulation group was the smallest, and the number of metastases in the IRF1 downregulation group was the largest. When lung tissues were cut, there were isolated metastatic lung nodules in 1 mouse in the shRNA-IRF1 group (Figure 1B and C). Further pathological tissue H&E staining showed that the metastatic lesions in the IRF1 downregulation group were the largest, and the lesions in the IRF1 upregulation group were not obvious. In addition, no metastasis was observed in the IRF1 up-regulation group, while significant metastasis was observed in the IRF1 down-regulation group (Figure 1D). Immunohistochemical staining of tumor tissues and liver metastases showed that the expression of Bcl-2 protein in tumor tissues and liver metastases in the Ad-IRF1 group was lower than that in the Ad-NC group, while the expression of Bcl-2 in the IRF1 down-regulation group was the highest (Figure 1E). These research results indicate that IRF1 regulation affects the growth, metastasis and apoptosis-related protein Bcl-2 in vivo.

Figure 1. Overexpression of IRF1 promotes radiosensitivity of CRC to X-rays in vivo. (Xu X, et al., 2021)