长链非编码 RNA GLCC1 通过稳定 c-Myc 促进结直肠癌发生和葡萄糖代谢。

LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc.

机构信息

State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, 200001, Shanghai, China.

Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.

出版信息

Nat Commun. 2019 Aug 2;10(1):3499. doi: 10.1038/s41467-019-11447-8.

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 as LDHA, 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.

长链非编码 RNA（lncRNA）参与结直肠癌（CRC）的发生发展。然而，lncRNA 在 CRC 代谢中的作用，特别是在葡萄糖代谢中的作用仍知之甚少。在这项研究中，我们鉴定了一个 lncRNA，GLCC1，其在 CRC 细胞葡萄糖饥饿下显著上调，通过增强糖酵解来支持细胞存活和增殖。在机制上，GLCC1 通过与 HSP90 伴侣蛋白的直接相互作用稳定 c-Myc 转录因子免于泛素化，进而在 c-Myc 靶基因上特异地指定转录修饰模式，如 LDHA，从而重新编程 CRC 增殖的糖酵解代谢。临床上，GLCC1 与肿瘤发生、肿瘤大小相关，并预测预后不良。因此，GLCC1 在结直肠癌中具有致癌性。靶向 GLCC1 及其通路可能对治疗结直肠癌患者具有重要意义。