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KMID : 0620920220540070906
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Experimental & Molecular Medicine
2022 Volume.54 No. 7 p.906 ~ p.921
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Augmentation of the RNA m6A reader signature is associated with poor survival by enhancing cell proliferation and EMT across cancer types
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Oh Jae-Ik
Hwa Chan-Woong
Jang Dong-Jun
Shin Seung-Jae
Lee Soo-Jin
Kim Ji-Won
Lee Sang-Eun
Jung Hae-Rim
Oh Yu-Mi
Jang Gi-Yong
Kwon O-Bin
An Joon-Yong
Cho Sung-Yup
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Abstract
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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.
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KEYWORD
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Cancer genomics, Tumour biomarkers
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