M6A methylase related MCM3AP-AS1 promotes the progression of colorectal cancer through the miR-98/IGF2BP1 signaling axis

Abstract Background To investigate the relationship between N6-methyladenosine (m6A) related Long non-coding RNAs (lncRNAs) and prognosis in colon cancer (COAD) patients, and the effect of M6A methyltransferase RBM15 on downstream genes regulated by MCM3AP-AS1. Methods Download gene expression and clinical data from 552 COAD samples and 44 adjacent cancer samples from TCGA. Use the DESeq2 software package to screen differentially expressed genes (DEG) between COAD and adjacent cancer tissues. Calculate the correlation between m6A related genes and lncRNAs to screen for m6A related lncRNAs. Univariate Cox regression analysis is used to screen for m6A related lncRNAs that are significantly correlated with prognosis. Subsequently, LASSO was used to screen key lncRNAs from prognosis related lncRNAs to construct a risk model. CCK-8, Wound healing assay, Transwell assay, Flow cytometry, FISH assay, RNA pull-down, Double Luciferase activity assay and rescue experiment were used to explore the effect of MCM3AP-AS1 on colorectal cancer and its specific mechanism. Results Bioinformatics analysis constructed a risk model consisting of 12 lncRNAs. The prognosis of patients in the high-risk group is significantly lower than that in the low-risk group. The risk score has been proven to be an independent prognostic factor for COAD. Subsequently, a ceRNA network consisting of 8 m6A related lncRNAs, 23 miRNAs, and 1531 mRNA was established. Cell experiments have confirmed that the M6A methyltransferase RBM15 is significantly upregulated in colorectal cancer cells, which can mediate the regulation of miR-98 expression by MCM3AP-AS1. MCM3AP-AS1 is significantly upregulated in colorectal cancer cells, promoting cell proliferation, migration, invasion, and inhibiting cell apoptosis. The specific molecular mechanism may be to regulate the expression of IGF2BP1 by targeting downstream miR-98. Conclusion MCM3AP-AS1 can target miR-98 to regulate the expression of IGF2BP1, which may be a potential mechanism for the occurrence and development of colorectal cancer.