期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 1, 页码 30-42出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.65255
关键词
IRF7; Aerobic glycolysis; Warburg effect; Osteosarcoma; PKM2
资金
- National Natural Science Foundation of China [81903039]
- Shanghai Sailing Program [19YF1444500]
- Shanghai Excellent Young Medical Talents Training Program [2018YQ46]
- Shanghai Committee of Science and Technology [20ZR1451800]
- Shanghai Municipal Commission of Health and Family Planning [202040141]
This study reveals that IRF7 is downregulated in osteosarcoma and its higher expression is associated with a better survival prognosis. IRF7 plays critical roles in suppressing aerobic glycolysis in osteosarcoma cells through inhibition of PKM2 expression, making it a potential therapeutic target for osteosarcoma patients.
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.
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