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

Jiayin Tang, Tingting Yan, Yujie Bao, Chaoqin Shen, Chenyang Yu, Xiaoqiang Zhu, Xianglong Tian, Fangfang Guo, Qian Liang, Qiang Liu, Ming Zhong, Jinxian Chen, Zhizheng Ge, Xiaobo Li, Xiaoyu Chen, Yun Cui, Yingxuan Chen, Weiping Zou, Haoyan Chen (), Jie Hong () and Jing-Yuan Fang ()
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Jiayin Tang: Shanghai Jiao Tong University
Tingting Yan: Shanghai Jiao Tong University
Yujie Bao: Shanghai Jiao Tong University
Chaoqin Shen: Shanghai Jiao Tong University
Chenyang Yu: Shanghai Jiao Tong University
Xiaoqiang Zhu: Shanghai Jiao Tong University
Xianglong Tian: Shanghai Jiao Tong University
Fangfang Guo: Shanghai Jiao Tong University
Qian Liang: Shanghai Jiao Tong University
Qiang Liu: Shanghai Jiao Tong University School of Medicine
Ming Zhong: Shanghai Jiao Tong University
Jinxian Chen: Shanghai Jiao Tong University
Zhizheng Ge: Shanghai Jiao Tong University
Xiaobo Li: Shanghai Jiao Tong University
Xiaoyu Chen: Shanghai Jiao Tong University
Yun Cui: Shanghai Jiao Tong University
Yingxuan Chen: Shanghai Jiao Tong University
Weiping Zou: University of Michigan School of Medicine
Haoyan Chen: Shanghai Jiao Tong University
Jie Hong: Shanghai Jiao Tong University
Jing-Yuan Fang: Shanghai Jiao Tong University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11447-8

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