Comprehensive Analysis of Differentially Expressed Profiles of mRNA N6-Methyladenosine in Colorectal Cancer

Abstract

Aim: To comprehensively profile the landscape of the mRNA N6-methyladenosine (m6A) modification in human colorectal cancer (CRC).Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was explored to compare the difference in mRNA N6-methyladenosine (m6A) methylation between CRC tissues and adjacent normal control (NC) tissue. RNA-sequencing (RNA-seq) was performed to transcribe differentially expressed mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq data was conducted to predict RNA-binding proteins (RBPs).Results: MeRIP-seq identified 1110 differentially m6A methylated sites (DMMSs) and 980 differentially m6A methylated genes (DMMGs) in CRC, with 50.13% of all modified genes showing unique m6A-modified peaks in CRC. RNA-seq showed 915 upregulated genes and 1463 downregulated genes in CRC. QRT-PCR verified the RNA-seq results by detecting the expression of some mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq identified 400 differentially m6A methylated and expressed genes (DEGs), and pathway analysis detected that DMMGs and DEGs were closely related to cancer. After analyzing these DMMGs and DEGs through the GEPIA database, we found that the expression of B3GNT6, DKC1, SRPK1, and RIMKLB were associated with prognosis, and the expression of B3GNT6 and RIMKLB were associated with clinical stage. 17 RBPs were identified based on the DMMGs and DEGs, among which FXR1, FXR2, FMR1, IGF2BP2, IGF2BP3, and SRSF1 were obviously highly expressed in CRC, and FMR1, IGF2BP2, and IGF2BP3 were closely related to methylation, and might be involved in the development of CRC.Conclusion: This study comprehensively profiled m6A modification of mRNAs in CRC, which revealed possible mechanisms of m6A-mediated gene expression regulation.

IGF2BP2 promotes pancreatic carcinoma progression by enhancing the stability of B3GNT6 mRNA via m6A methylation

“…B3GNT6 is a beta‐1,3‐N‐acetylglucosaminyl transferase that adds an N‐acetylglucosamine moiety to N‐acetylgalactosamine‐modified serine or threonine residues to affect biosynthesis and metabolism. Studies have found that B3GNT6 is closely related to a variety of disease processes, such as immunity deficiency, 21 colorectal cancer and m6A modification, 22 Together, these results indicate that B3GNT6 may be the downstream target of IGF2BP2. Survival analysis with TCGA data showed high B3GNT6 was related to lower survival status, and Spearman correlation analysis also showed the co‐expression of IGF2BP2 and B3GNT6 (Figure 5E ).…”

Identification of a novel lymphangiogenesis signature associated with immune cell infiltration in colorectal cancer based on bioinformatics analysis

“…RimK-like family member B (RIMKLB) is an enzyme that post-translationally modulates ribosomal protein S6 and contributes to the regulation of immune cell development [ 57 ]. RIMKLB has been identified as a prognostic biomarker in CRC [ 58 – 61 ]. Our results were consistent with previous findings.…”

Analysis of the Prognostic Significance and Immune Infiltration of the Amino Acid Metabolism-Related Genes in Colon Adenocarcinoma

“…Finally, nine prognostic related genes were obtained to establish a risk model. Among the nine genes, ribosomal modification protein rimK like family member B (RIMKLB) is a protein-coding gene involved in the glutamine family amino acid metabolic process and cellular protein modification process, which is proved to be associated with prognosis and clinical stage ( Li et al, 2021 ). Asparaginase (ASPG) is known to be related to asparagine degradation.…”