Conclusions
Our findings suggest that m6A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.
Methods
Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used. Gene alteration and pathway analysis were done in cBioportal. The protein network of m6A regulators and its related pathway members was analyzed in STRING online platform. Phylogenetic tree was constructed in MEGA7. m6A modification sites were predicted by SRAMP. m6A related SNPs were analyzed by m6ASNP. The modulation of m6A on its related pathway members was validated by m6A-seq, real-time PCR and phosphor-MAPK array.
Results
We found that m6A regulators were mostly upregulated in GI cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m6A modification in most human cancers, including GI cancer, which was further verified by m6A-Seq and phospho-MAPK array. Conclusions: Our findings suggest that m6A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.