IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.
IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.
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IRF7 通过抑制骨肉瘤中 PKM2 的转录抑制 Warburg 效应
DOI：
10.7150/ijbs.65255
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发表时间：
2022
影响因子：
9.2
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Li Z;Geng M;Ye X;Ji Y;Li Y;Zhang X;Xu W
骨肉瘤（OS）是一种发生于青少年和年轻人的恶性骨肿瘤。IRF 7属于干扰素调节因子（IRFs）的转录因子家族，并且先前已被描述为在多种癌症类型中起肿瘤抑制剂的作用。然而，IRF 7在OS中的生物学功能和细胞机制仍不清楚。本研究通过实时荧光定量PCR（qRT-PCR）和蛋白质印迹法发现，IRF 7在OS中表达下调，且IRF 7的高表达与较好的生存预后相关。此外，功能丧失和功能获得研究已经证明IRF 7在抑制骨肉瘤细胞有氧糖酵解中的关键功能，如葡萄糖摄取、乳酸产生、细胞外酸化速率和耗氧速率所证明的。IRF 7通过直接转录调控抑制糖酵解关键基因PKM 2的表达。此外，在体外和体内的肿瘤抑制作用的IRF 7在OS中被发现，这些作用在很大程度上是糖酵解依赖性的。因此，我们的研究揭示了IRF 7在葡萄糖代谢重编程中前所未有的作用，并表明IRF 7可能作为OS患者的潜在治疗靶点。
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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影响因子：
3.7
作者：
Li Q;Tainsky MA
通讯作者：
Tainsky MA
影响因子：
37.3
作者：
Shen S;Yao T;Xu Y;Zhang D;Fan S;Ma J
通讯作者：
Ma J
影响因子：
3.9
作者：
Rathore R;Van Tine BA
通讯作者：
Van Tine BA
血清素信号传导增加有助于代谢应激下胰腺肿瘤细胞的 Warburg 效应，并促进小鼠胰腺肿瘤的生长
影响因子：
29.4
作者：
Jiang, Shu-Heng;Li, Jun;Zhang, Zhi-Gang
通讯作者：
Zhang, Zhi-Gang
影响因子：
20.3
作者：
Asslaber, Daniela;Qi, Yuan;Egle, Alexander
通讯作者：
Egle, Alexander