FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m 6 A-dependent manner

FMR1, a new m A 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 ce...

Full description

Saved in:
Bibliographic Details
Published in:Cell death & disease 2022-11, Vol.13 (11), p.941
Main Authors: Hu, Yuhan, Gao, Qingzu, Ma, Shuai, Yu, Pei, Ding, Shuang, Yao, Xiaofei, Zhang, Zheying, Lu, Shuya, Lu, Manman, Zhang, Jinghang, Wang, Yanling, Qian, Xinlai, Zhong, Jiateng
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell Proliferation - genetics
Colorectal Neoplasms - pathology
ErbB Receptors - genetics
ErbB Receptors - metabolism
Fragile X Mental Retardation Protein - genetics
Gene Expression Regulation, Neoplastic
Humans
Methyltransferases - metabolism
RNA, Messenger - genetics
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:FMR1, a new m A 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 m A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m A-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.
ISSN:2041-4889