Abstract: OBJECTIVE: To investigate m⁶A methylation levels of mRNAs which are related to glycidyl methacrylate (GMA)-induced malignant transformation of 16HBE cells and their functional roles. METHODS: After 16HBE cells were repeatedly exposed to GMA(8 μg/mL),the 30th generation cells of GMA group and DMSO control group were collected. m⁶A methylation levels of mRNAs which were related to 16HBE malignant transformation were detected by high-throughput human apparent transcriptome chip. The differentially m⁶A-methylated mRNAs and differentially expressed mRNAs were screened by Visual Studio Code. The Omicshare tools were used for GO enrichment and KEGG pathway analyses of these mRNAs. RESULTS: A total of 454 lncRNAs with differential m⁶A methylation were identified in GMA-induced 16HBE malignant transformed cells,including 334 which were hypermethylated mRNAs and 120 which were hypomethylated mRNAs (|FC|>2.0,P<0.05). There was a total of 434 differentially expressed mRNAs,among which 236 were up-regulated and 198 were down-regulated (|FC|>2.0,P<0.05). There were 45 m⁶A-methylated mRNAs. The GO analyses showed that SNAP receptor activity,SNARE binding and SNARE complex were the main biological processes. KEGG pathway analyses showed that m⁶A-methylated mRNAs were enriched in SNARE interactions in vesicular transport,non-homologous end-joining,and phenylalanine metabolism. CONCLUSION: Our data indicate that m⁶A methylation played an important role in the process of GMA-induced 16HBE malignant transformation.

Key words: N⁶-methyladenosine, glycidyl methacrylate, high throughput microarray, malignant transformation