Abstract

FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.

Details

Title
FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m6A-dependent manner
Author
Hu, Yuhan 1 ; Gao, Qingzu 2 ; Ma, Shuai 3 ; Yu, Pei 3 ; Ding, Shuang 3 ; Yao, Xiaofei 3 ; Zhang, Zheying 3 ; Lu, Shuya 3 ; Lu, Manman 3 ; Zhang, Jinghang 2 ; Wang, Yanling 4 ; Qian, Xinlai 5 ; Zhong, Jiateng 6   VIAFID ORCID Logo 

1  Xinxiang Medical University, Department of Pathology, School of Basic Medical Sciences, Xinxiang, China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X); The First Affiliated Hospital of Xinxiang Medical University, Department of Pathology, Xinxiang, China (GRID:grid.493088.e) (ISNI:0000 0004 1757 7279); Xinxiang Medical University, Micromorphology Laboratory, School of Basic Medical Sciences, Xinxiang, China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X) 
2  The First Affiliated Hospital of Xinxiang Medical University, Department of Pathology, Xinxiang, China (GRID:grid.493088.e) (ISNI:0000 0004 1757 7279) 
3  Xinxiang Medical University, Department of Pathology, School of Basic Medical Sciences, Xinxiang, China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X) 
4  The Third Affiliated Hospital of Sun Yat-sen University, Department of Anesthesiology, Guangzhou, China (GRID:grid.412558.f) (ISNI:0000 0004 1762 1794) 
5  Xinxiang Medical University, Department of Pathology, School of Basic Medical Sciences, Xinxiang, China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X); The Third Affiliated Hospital of Xinxiang Medical University, Department of Pathology, Xinxiang, P.R. China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X) 
6  Xinxiang Medical University, Department of Pathology, School of Basic Medical Sciences, Xinxiang, China (GRID:grid.412990.7) (ISNI:0000 0004 1808 322X); The First Affiliated Hospital of Xinxiang Medical University, Department of Pathology, Xinxiang, China (GRID:grid.493088.e) (ISNI:0000 0004 1757 7279) 
Publication year
2022
Publication date
Nov 2022
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-022-05391-7
ProQuest document ID
2733868735
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.