N6-Methyladenosine (m6A) RNA modification plays a critical role in the posttranscriptional regulation of gene expression. Alterations in cellular m6A levels and m6A-related genes have been reported in many cancers, but whether they play oncogenic or tumor-suppressive roles is inconsistent across cancer types. We investigated common features of alterations in m6A modification and m6A-related genes during carcinogenesis by analyzing transcriptome data of 11 solid tumors from The Cancer Genome Atlas database and our in-house gastric cancer cohort. We calculated m6A writer (W), eraser (E), and reader (R) signatures based on corresponding gene expression. Alterations in the W and E signatures varied according to the cancer type, with a strong positive correlation between the W and E signatures in all types. When the patients were divided according to m6A levels estimated by the ratio of the W and E signatures, the prognostic effect of m6A was inconsistent according to the cancer type. The R and especially the R2 signatures (based on the expression of IGF2BPs) were upregulated in all cancers. Patients with a high R2 signature exhibited poor prognosis across types, which was attributed to enrichment of cell cycle- and epithelial–mesenchymal transition-related pathways. Our study demonstrates common features of m6A alterations across cancer types and suggests that targeting m6A R proteins is a promising strategy for cancer treatment.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Nos. 2019M3E5D3073568, 2021R1A2C3008021 and 2021R1A4A1029097); the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT (Grant No. 2018M3A9F3056902); the Creative-Pioneering Researchers Program through Seoul National University (Grant No. 800-20200510); the New Faculty Startup Fund from Seoul National University (Grant No. 800-20210282); and the Korea University Grant (K2200991). D.J., S.S., S.-J.L., J.K., S.E.L., and C.H. received a scholarship from the BK21 FOUR education program.
© 2022, The Author(s).
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry