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多种人类组织发育和癌症过程中mA调控因子的动态表达

Dynamic Expression of mA Regulators During Multiple Human Tissue Development and Cancers.

作者信息

Zhang Ya, Xu Sicong, Xu Gang, Gao Yueying, Li Si, Zhang Ke, Tian Zhanyu, Guo Jing, Li Xia, Xu Juan, Li Yongsheng

机构信息

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou, China.

College of Biomedical Information and Engineering, Hainan Medical University, Haikou, China.

出版信息

Front Cell Dev Biol. 2021 Jan 26;8:629030. doi: 10.3389/fcell.2020.629030. eCollection 2020.

DOI:10.3389/fcell.2020.629030
PMID:33575259
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7870680/
Abstract

N6-methyladenosine (mA) plays critical roles in human development and cancer progression. However, our knowledge regarding the dynamic expression of mA regulators during human tissue development is still lacking. Here, we comprehensively analyzed the dynamic expression alterations of mA regulators during seven tissue development and eight cancer types. We found that mA regulators globally exhibited decreased expression during development. In addition, IGF2BP1/2/3 (insulinlike growth factor 2 MRNA-binding protein 1/2/3) exhibited reverse expression pattern in cancer progression, suggesting an oncofetal reprogramming in cancer. The expressions of IGF2BP1/2/3 were regulated by genome alterations, particularly copy number amplification in cancer. Clinical association analysis revealed that higher expressions of IGF2BP1/2/3 were associated with worse survival of cancer patients. Finally, we found that genes significantly correlated with IGF2BP1/2/3 were significantly enriched in cancer hallmark-related pathways. In summary, dynamic expression analysis will guide both mechanistic and therapeutic roles of mA regulators during tissue development and cancer progression.

摘要

N6-甲基腺苷（mA）在人类发育和癌症进展中起着关键作用。然而，我们对人类组织发育过程中mA调节因子的动态表达仍缺乏了解。在此，我们全面分析了七种组织发育和八种癌症类型中mA调节因子的动态表达变化。我们发现，在发育过程中，mA调节因子的表达整体呈现下降趋势。此外，IGF2BP1/2/3（胰岛素样生长因子2 mRNA结合蛋白1/2/3）在癌症进展中呈现相反的表达模式，提示癌症中存在一种肿瘤胎儿重编程现象。IGF2BP1/2/3的表达受基因组改变调控，尤其是癌症中的拷贝数扩增。临床关联分析显示，IGF2BP1/2/3的高表达与癌症患者较差的生存率相关。最后，我们发现与IGF2BP1/2/3显著相关的基因在癌症特征相关通路中显著富集。总之，动态表达分析将为mA调节因子在组织发育和癌症进展中的机制及治疗作用提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/68d69ad67531/fcell-08-629030-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/5e07f648b21d/fcell-08-629030-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/7c86ff908aa7/fcell-08-629030-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/a48eab4c03ab/fcell-08-629030-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/0344d4a1c9cb/fcell-08-629030-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/68d69ad67531/fcell-08-629030-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/5e07f648b21d/fcell-08-629030-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/7c86ff908aa7/fcell-08-629030-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/a48eab4c03ab/fcell-08-629030-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/0344d4a1c9cb/fcell-08-629030-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b596/7870680/68d69ad67531/fcell-08-629030-g0005.jpg

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RNA N-Methyladenosine Methyltransferase METTL3 Facilitates Colorectal Cancer by Activating the mA-GLUT1-mTORC1 Axis and Is a Therapeutic Target.
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