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

• Published in: Nature communications Vol. 10; no. 1; pp. 3499 - 15
• Main Authors: Tang, Jiayin, Yan, Tingting, Bao, Yujie, Shen, Chaoqin, Yu, Chenyang, Zhu, Xiaoqiang, Tian, Xianglong, Guo, Fangfang, Liang, Qian, Liu, Qiang, Zhong, Ming, Chen, Jinxian, Ge, Zhizheng, Li, Xiaobo, Chen, Xiaoyu, Cui, Yun, Chen, Yingxuan, Zou, Weiping, Chen, Haoyan, Hong, Jie, Fang, Jing-Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.08.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/51; 13/89; 14/105; 38/15; 38/39; 38/47; 631/67/1504; 631/67/2327; 82/58; 82/80; Aged; Animals; c-Myc protein; Cancer; Carcinogenesis; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogens; Cell Line, Tumor; Cell Proliferation; Cell survival; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Female; Gene Expression Regulation, Neoplastic; Glucose; Glucose - metabolism; Glycolysis; Glycolysis - genetics; HSP90 Heat-Shock Proteins - genetics; Hsp90 protein; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase - genetics; L-Lactate Dehydrogenase - metabolism; Male; Medical prognosis; Metabolism; Mice; Middle Aged; multidisciplinary; Myc protein; Prognosis; Proto-Oncogene Proteins c-myc - metabolism; RNA, Long Noncoding - metabolism; Science; Science (multidisciplinary); Starvation; Tumorigenesis; Ubiquitination; Ubiquitination - genetics; Up-Regulation; Xenograft Model Antitumor Assays
• ISSN: 2041-1723; 2041-1723
• 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. lncRNA and cellular metabolism are frequently dysregulated in cancer. In this study, the authors discover the lncGLCC1 is increased in colorectal cancer cells under glucose starvation conditions and correlates with poor prognosis in this cancer.