LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc
LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc
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LncRNA GLCC1通过稳定c-Myc促进结直肠癌发生和葡萄糖代谢
DOI：
10.1038/s41467-019-11447-8
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发表时间：
2019-08-02
影响因子：
16.6
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
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作者：
Tang, Jiayin;Yan, Tingting;Fang, Jing-Yuan
长非编码RNA(LncRNAs)与结直肠癌(CRC)有关。然而，lncRNAs在结直肠癌代谢，尤其是葡萄糖代谢中的作用仍然很大程度上是未知的。在这项研究中，我们鉴定了一种lncRNA，GLCC1，它在葡萄糖饥饿的情况下在CRC细胞中显著上调，通过促进糖酵解来支持细胞的生存和增殖。在机制上，GLCC1通过与HSP90分子伴侣的直接相互作用稳定c-Myc转录因子的泛素化，并进一步指定c-Myc靶基因如LDHA的转录修饰模式，从而重新编程糖酵解代谢以促进结直肠癌的增殖。临床上，GLCC1与肿瘤的发生、大小及预后不良有关。因此，GLCC1在结直肠癌中具有机制、功能和临床致癌作用。靶向GLCC1及其通路对结直肠癌患者的治疗可能具有重要意义。
Long non-coding RNAs (lncRNAs) contribute to colorectal cancer (CRC). However, the role of lncRNAs in CRC metabolism, especially glucose metabolism remains largely unknown. In this study, we identify a lncRNA, GLCC1, which is significantly upregulated under glucose starvation in CRC cells, supporting cell survival and proliferation by enhancing glycolysis. Mechanistically, GLCC1 stabilizes c-Myc transcriptional factor from ubiquitination by direct interaction with HSP90 chaperon and further specifies the transcriptional modification pattern on c-Myc target genes, such asLDHA, consequently reprogram glycolytic metabolism for CRC proliferation. Clinically, GLCC1 is associated with tumorigenesis, tumor size and predicts poor prognosis. Thus, GLCC1 is mechanistically, functionally, and clinically oncogenic in colorectal cancer. Targeting GLCC1 and its pathway may be meaningful for treating patients with colorectal cancer.