Mechanistically, we mainly elucidated that the low RAB5A mRNA level by ALKBH5 knockdown was due to the accelerated decay of RAB5A mRNA depending on m6A reader protein YTHDF2, decreasing the RAB5A protein level as a result, and RAB5A, a member of RAS oncogene family, was subsequently identified as a key oncogenic driver in CRC. Here, ALKBH5 is linked to colorectal carcinoma.