Integrated analysis of transcriptome-wide m6A methylome of human lung adenocarcinoma A549 cells enriched by Interleukin 37 treatment

N6-methyladenosine (m6A) is an important epitranscriptomic mark with high abundance in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer formation and metastasis. IL-37 plays a crucial protective role in lung cancer. In our previous studies we found that IL-37 has been identified as a potential novel tumor suppressor by suppressing STAT3 activation and decreasing epithelialto-mesenchymal transition via inhibiting IL-6 expression. Moreover, we found the treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered distinct features of continuous and temporal-specific m6A methylation across the the treatment of IL-37 on A549 cell line. Temporal-specific m6A peaks exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO after the treatment of IL-37 on A549 cells and lung cancer tissues. In addition, we found that increased expression of ALKBH5, lead to increased proliferation and tumorigenicity of A549 cells, likely through activation of theWnt5a/5b pathway. Together, our findings provide evidence that RNA m6A methylation is controlled in the treatment of IL-37 on lung cancer cells.