磷酸戊糖途径
癌症研究
转移
结直肠癌
氧化磷酸化
生物
肝癌
信号转导
PI3K/AKT/mTOR通路
癌症
化学
糖酵解
细胞生物学
生物化学
遗传学
新陈代谢
肝细胞癌
作者
Ming Yuan,Xinsheng Zhang,Fangxia Yue,Feifan Zhang,Sufen Jiang,Chao Wang,Jinjuan Lv,Zhenyu Zhang,Yuzhu Sun,Zihao Chen,Han Wu,Xiaoqian Liu,Xiao‐Qi Yu,Bin Wei,Kexin Jiang,Fang Lin,Yunfei Zuo,Shuo Ren
标识
DOI:10.1002/advs.202205229
摘要
Abstract 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.
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