Augmentation of the RNA m6A reader signature is associated with poor survival by enhancing cell proliferation and EMT across cancer types

Jaeik Oh, Chanwoong Hwa, Dongjun Jang, Seungjae Shin, Soo Jin Lee, Jiwon Kim, Sang Eun Lee, Hae Rim Jung, Yumi Oh, Giyong Jang, Obin Kwon, Joon Yong An, Sung Yup Cho

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)906-921
Number of pages16
JournalExperimental and Molecular Medicine
Volume54
Issue number7
DOIs
Publication statusPublished - 2022 Jul

Bibliographical note

Funding 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.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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