CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway

• Published in: Advanced science Vol. 10; no. 33; pp. e2205229 - n/a
• Main Authors: Yuan, Menglang, Zhang, Xinsheng, Yue, Fangxia, Zhang, Feifan, Jiang, Sufen, Zhou, Xu, Lv, Jinjuan, Zhang, Zhenyu, Sun, Yuzhu, Chen, Zihao, Wu, Han, Liu, Xiaoqian, Yu, Xiaoqi, Wei, Bowen, Jiang, Kexin, Lin, Fang, Zuo, Yunfei, Ren, Shuangyi
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.11.2023; Wiley
• Subjects: AZGP1; circNOLC1; Colorectal cancer; Genes; Genomes; Glucose; Kinases; Liver; Metabolism; Metastasis; miR‐212‐5p; oxidative pentose phosphate pathway; Proteins; Signal transduction
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202205229

Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway‐associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway‐related intermediate metabolites and elevates NADP+/NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR‐212‐5p to upregulate c‐Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR‐212‐5p/c‐Met axis plays a key role in oxidative pentose phosphate pathway‐mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer. Liver metastasis is a common cause of death in progressive colorectal cancer patients. This study identifies a novel pathway underlying colorectal cancer liver metastasis by circNOLC1‐mediated oxidative pentose phosphate pathway reprogramming. This effect is achieved by circNOLC1 interacting with AZGP1 and sponging miR‐212‐5p to induce G6PD activity, which can provide a novel target for precision medicine of colorectal cancer.