FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m6A-dependent manner

• DOI: 10.1038/s41419-022-05391-7
• Publication Date: 2022-11-08T17:13:22Z
• Authors: Yuhan Hu; Qingzu Gao; Shuai Ma; Pei Yu; Shuang Ding; Xiaofei Yao; Zheying Zhang; Shuya Lu; Manman Lu; Jinghang Zhang; Yanling Wang; Xinlai Qian; Jiateng Zhong
• Keywords: Gene Expression Regulation, Neoplastic; ErbB Receptors; Fragile X Mental Retardation Protein; QH573-671; Cell Line, Tumor; Humans; RNA, Messenger; Methyltransferases; Cytology; Colorectal Neoplasms; Article; Cell Proliferation; 3. Good health

AbstractFMR1, 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.