m6A-modified LINC02418 induces transcriptional and post-transcriptional modification of CTNNB1 via interacting with YBX1 and IGF2BP1 in colorectal cancer.

Colorectal cancer (CRC) represents a significant menace to human health, but its molecular pathogenesis remains unclear. Herein, we explored the functional role of LINC02418 in CRC progression. The function of LINC02418 in CRC was determined through vitro and in vivo experiments. The molecular mechanism of LINC02418 in CRC was explored by quantitative real-time PCR (qPCR) analyses, western blot, luciferase reporter assay, methylated RNA immunoprecipitation (MeRIP) assay, RNA pull-down, RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. The results revealed that LINC02418 expression was upregulated in CRC tissues and the high expression of LINC02418 was related to unfavorable survival of CRC patients. Besides, knockdown of LINC02418 expression resulted in the inhibition of proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, we found METTL3-mediated m6A modification induced the aberrant expression of LINC02418 in CRC. LINC02418 could interact with YBX1 and enhance YBX1 DNA-binding ability to the CTNNB1 promoter, resulting in transcriptional activation of CTNNB1. In the post-transcriptional stage, LINC02418 could also enhance CTNNB1 stability by promoting the interaction between IGF2BP1 protein and CTNNB1 mRNA. What is more, LINC02418 expression could be transcriptionally enhanced by YBX1 protein. Collectively, this study unveils a novel oncogenic mechanism for LINC02418 in CRC and the LINC02418 might be a novel therapeutic target in CRC treatment.