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

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 liv...

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Main Authors: Menglang Yuan, Xinsheng Zhang, Fangxia Yue, Feifan Zhang, Sufen Jiang, Xu Zhou, Jinjuan Lv, Zhenyu Zhang, Yuzhu Sun, Zihao Chen, Han Wu, Xiaoqian Liu, Xiaoqi Yu, Bowen Wei, Kexin Jiang, Fang Lin, Yunfei Zuo, Shuangyi Ren
Format: Article
Language:English
Published: Wiley 2023-11-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202205229
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author Menglang Yuan
Xinsheng Zhang
Fangxia Yue
Feifan Zhang
Sufen Jiang
Xu Zhou
Jinjuan Lv
Zhenyu Zhang
Yuzhu Sun
Zihao Chen
Han Wu
Xiaoqian Liu
Xiaoqi Yu
Bowen Wei
Kexin Jiang
Fang Lin
Yunfei Zuo
Shuangyi Ren
author_facet Menglang Yuan
Xinsheng Zhang
Fangxia Yue
Feifan Zhang
Sufen Jiang
Xu Zhou
Jinjuan Lv
Zhenyu Zhang
Yuzhu Sun
Zihao Chen
Han Wu
Xiaoqian Liu
Xiaoqi Yu
Bowen Wei
Kexin Jiang
Fang Lin
Yunfei Zuo
Shuangyi Ren
author_sort Menglang Yuan
collection DOAJ
description 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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spelling doaj.art-ea8ea52642304cca981d3b68fff45f362023-11-24T08:40:29ZengWileyAdvanced Science2198-38442023-11-011033n/an/a10.1002/advs.202205229CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate PathwayMenglang Yuan0Xinsheng Zhang1Fangxia Yue2Feifan Zhang3Sufen Jiang4Xu Zhou5Jinjuan Lv6Zhenyu Zhang7Yuzhu Sun8Zihao Chen9Han Wu10Xiaoqian Liu11Xiaoqi Yu12Bowen Wei13Kexin Jiang14Fang Lin15Yunfei Zuo16Shuangyi Ren17Department of General Surgery The Second Hospital of Dalian Medical University 116023 Dalian ChinaDepartment of General Surgery The Second Hospital of Dalian Medical University 116023 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of General Surgery The Second Hospital of Dalian Medical University 116023 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of General Surgery The Second Hospital of Dalian Medical University 116023 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of Clinical Biochemistry College of Laboratory Diagnostic Medicine Dalian Medical University 116044 Dalian ChinaDepartment of General Surgery The Second Hospital of Dalian Medical University 116023 Dalian ChinaAbstract 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.https://doi.org/10.1002/advs.202205229AZGP1circNOLC1miR‐212‐5poxidative pentose phosphate pathway
spellingShingle Menglang Yuan
Xinsheng Zhang
Fangxia Yue
Feifan Zhang
Sufen Jiang
Xu Zhou
Jinjuan Lv
Zhenyu Zhang
Yuzhu Sun
Zihao Chen
Han Wu
Xiaoqian Liu
Xiaoqi Yu
Bowen Wei
Kexin Jiang
Fang Lin
Yunfei Zuo
Shuangyi Ren
CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
Advanced Science
AZGP1
circNOLC1
miR‐212‐5p
oxidative pentose phosphate pathway
title CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
title_full CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
title_fullStr CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
title_full_unstemmed CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
title_short CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR‐212‐5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway
title_sort circnolc1 promotes colorectal cancer liver metastasis by interacting with azgp1 and sponging mir 212 5p to regulate reprogramming of the oxidative pentose phosphate pathway
topic AZGP1
circNOLC1
miR‐212‐5p
oxidative pentose phosphate pathway
url https://doi.org/10.1002/advs.202205229
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