Abstract / Summary
Fasting, with short term starvation (STS) included, attracts wide attention in the treatment of colorectal cancer (CRC) due to its excellent antitumor efficacy and its safety, feasibility, and cost-effectiveness. However, the specific mechanism of fasting induced tumor suppression remains largely uncovered. Bioinformatic analysis was combined with in vitro experiments using STS-treated CRC cells to identify the interferon regulatory factor IRF7 and its expression was validated in clinical samples. The functional role of IRF7 was assessed through knockdown experiments, followed by series of in vitro assays. Signaling pathways were analyzed by Western blot. Orthotopic transplantation mouse models were employed to validate the results. A notable upregulation of IRF7 in CRC cells following STS treatment was demonstrated by bioinformatic analysis and corresponding in vitro experiments, further corroborated by clinical samples. The knockdown of IRF7 led to enhanced proliferation of CRC cells and a decrease in cell death upon STS treatment. Specifically, IRF7 inhibited the proliferation of CRC cells by downregulating PFKFB3 while facilitating the apoptosis of CRC cells through the induction of type I interferon production. Moreover, correlation analysis and in vitro experiments revealed that IRF7 acts as a downstream effector of STAT1 and can reciprocally upregulate STAT1 under STS treatment, suggesting potential positive feedback that exerts tumor-suppressive effects on CRC in the context of STS treatment. This study uncovered the elevation and function of IRF7 in CRC after STS and explored its interaction with glucose metabolism and type I interferon, providing a potential therapeutic target for CRC treatment in clinical practice.