Zhang Pengfei, Cao Limian, Fan Pingsheng, Mei Yide, Wu Mian
CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China.
Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, China.
EMBO Rep. 2016 Aug;17(8):1204-20. doi: 10.15252/embr.201642067. Epub 2016 Jun 17.
The c-Myc proto-oncogene is activated in more than half of all human cancers. However, the precise regulation of c-Myc protein stability is unknown. Here, we show that the lncRNA-MIF (c-Myc inhibitory factor), a c-Myc-induced long non-coding RNA, is a competing endogenous RNA for miR-586 and attenuates the inhibitory effect of miR-586 on Fbxw7, an E3 ligase for c-Myc, leading to increased Fbxw7 expression and subsequent c-Myc degradation. Our data reveal the existence of a feedback loop between c-Myc and lncRNA-MIF, through which c-Myc protein stability is finely controlled. Additionally, we show that the lncRNA-MIF inhibits aerobic glycolysis and tumorigenesis by suppressing c-Myc and miR-586.
c-Myc原癌基因在超过半数的人类癌症中被激活。然而，c-Myc蛋白稳定性的确切调控机制尚不清楚。在此，我们表明lncRNA-MIF（c-Myc抑制因子），一种由c-Myc诱导的长链非编码RNA，是miR-586的竞争性内源RNA，它减弱了miR-586对Fbxw7（一种c-Myc的E3连接酶）的抑制作用，导致Fbxw7表达增加及随后的c-Myc降解。我们的数据揭示了c-Myc与lncRNA-MIF之间存在一个反馈环，通过该反馈环可精细调控c-Myc蛋白的稳定性。此外，我们表明lncRNA-MIF通过抑制c-Myc和miR-586来抑制有氧糖酵解和肿瘤发生。
