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

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.

Expression of pyroptosis-related genes are correlated with immune microenvironment and predict prognosis in ESCA

“…Fragile X mental retardation 1 (FMR1) has been identified as a new immune-related prognostic biomarker for renal clear cell carcinoma (Wu et al 2022 ). In addition, FMR1 can promote the development of colorectal cancer cells by stabilizing EGFR mRNA (Hu et al 2022 ). Studies have shown that FMR1 is closely related to the prognosis of various tumors.…”

m6A modification on the fate of colorectal cancer: functions and mechanisms of cell proliferation and tumorigenesis

“…However, whether hnRNPA2B1 promotes CRC cell proliferation in an m6A-dependent manner or not has not been elucidated. FMR1, a new m6A reader, is known to recognize the m6A-modification site in EGFR mRNA, sustain its stability, and maintain its expression in an m6Adependent manner, thereby prohibiting apoptosis and promoting the cell-cycle progression of CRC cells (87).…”

Biological landscape and nanostructural view in development and reversal of oxaliplatin resistance in colorectal cancer

“…The overexpression of IGF2BP2 promotes TFRC expression and facilitates the metabolism of iron in accelerating CRC malignancy [19] . Noteworthy, through m6A-dependent mechanism, FMR1 upregulates the stability of EGFR to enhance the tumorigenesis in colorectal cancer [20] . TNF-α upregulates USP14 expression that is vital for increasing JNK levels and developing feedback loop in promoting tumorigenesis [21] .…”