CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress
CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress
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CircACC1 在代谢应激下调节 AMPK 复合物的组装和激活
DOI：
10.1016/j.cmet.2019.05.009
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发表时间：
2019-07-02
期刊：
影响因子：
29
通讯作者：
Wu, Mian
中科院分区：
文献类型：
--
作者：
Li, Qidong;Wang, Yichun;Wu, Mian
我们报道circACC1，一种源自人类ACC1的环状RNA，在细胞对代谢应激的反应中起关键作用。CircACC1比ACC1优先产生，以响应转录因子c-Jun的血清剥夺。它通过与调节的β和γ亚基形成三元配合物来稳定和促进AMPK全酶的酶活性。circACC1的细胞水平调节脂肪酸β -氧化和糖酵解，导致细胞脂质储存的深刻变化。在异种肿瘤移植模型中，沉默或强制表达circACC1分别导致生长抑制和增强。此外，结直肠癌组织中AMPK激活的增加通常与circACC1表达的升高相关。我们得出结论，circACC1是引发AMPK激活的经济手段，并且提出癌细胞在代谢重编程过程中利用circACC1。
We report that circACC1, a circular RNA derived from human ACC1, plays a critical role in cellular responses to metabolic stress. CircACC1 is preferentially produced over ACC1 in response to serum deprivation by the transcription factor c-Jun. It functions to stabilize and promote the enzymatic activity of the AMPK holoenzyme by forming a ternary complex with the regulatory beta and gamma subunits. The cellular levels of circACC1 modulate both fatty acid beta-oxidation and glycolysis, resulting in profound changes in cellular lipid storage. In a tumor xenograft model, silencing or enforced expression of circACC1 resulted in growth inhibition and enhancement, respectively. Moreover, increased AMPK activation in colorectal cancer tissues was frequently associated with elevated circACC1 expression. We conclude that circACC1 serves as an economic means to elicit AMPK activation and moreover propose that cancer cells exploit circACC1 during metabolic reprogramming.