Int J Biol Sci 2022; 18(1):30-42. doi:10.7150/ijbs.65255 This issue

Research Paper

IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma

Zhikun Li1*, Mei Geng2*, Xiaojian Ye1*, Yunhan Ji1, Yifan Li1, Xiangyang Zhang1, Wei Xu1✉

1. Department of Orthopedics, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200336, China.
2. Department of Oncology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
*These authors contributed equally to this work.

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Citation:
Li Z, Geng M, Ye X, Ji Y, Li Y, Zhang X, Xu W. IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma. Int J Biol Sci 2022; 18(1):30-42. doi:10.7150/ijbs.65255. Available from https://www.ijbs.com/v18p0030.htm

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Abstract

Graphic abstract

Osteosarcoma (OS) is a malignant bone tumor among adolescents and young adults. IRF7 belongs to the transcription factor family of interferon regulatory factors (IRFs) and has previously been described to function as a tumor suppressor in multiple cancer types. However, the biological functions and cellular mechanism of IRF7 in OS remain elusive. In this study, by quantitative real-time PCR (qRT-PCR) and western blotting, we found that IRF7 was downregulated in OS, and the higher expression of IRF7 was correlated with a better survival prognosis. Moreover, loss-of-function and gain-of-function studies have proved the critical functions of IRF7 in suppressing aerobic glycolysis of osteosarcoma cells as evidenced by glucose uptake, lactate production, extracellular acidification rate, and oxygen consumption rate. Mechanistically, IRF7 inhibited the expression of key glycolytic gene PKM2 via direct transcriptional regulation. Moreover, the in vitro and in vivo tumor-suppressive roles of IRF7 were uncovered in OS and these effects were largely glycolysis-dependent. Therefore, our study unveils a previous unprecedented role of IRF7 in glucose metabolism reprogram and suggests that IRF7 might serve as a potential therapeutic target for patients with OS.

Keywords: IRF7, Aerobic glycolysis, Warburg effect, Osteosarcoma, PKM2