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Dynamic Expression of m⁶A Regulators During Multiple Human Tissue Development and Cancers.

ABSTRACT: N6-methyladenosine (m⁶A) plays critical roles in human development and cancer progression. However, our knowledge regarding the dynamic expression of m⁶A regulators during human tissue development is still lacking. Here, we comprehensively analyzed the dynamic expression alterations of m⁶A regulators during seven tissue development and eight cancer types. We found that m⁶A regulators globally exhibited decreased expression during development. In addition, IGF2BP1/2/3 (insulinlike growth factor 2 MRNA-binding protein 1/2/3) exhibited reverse expression pattern in cancer progression, suggesting an oncofetal reprogramming in cancer. The expressions of IGF2BP1/2/3 were regulated by genome alterations, particularly copy number amplification in cancer. Clinical association analysis revealed that higher expressions of IGF2BP1/2/3 were associated with worse survival of cancer patients. Finally, we found that genes significantly correlated with IGF2BP1/2/3 were significantly enriched in cancer hallmark-related pathways. In summary, dynamic expression analysis will guide both mechanistic and therapeutic roles of m⁶A regulators during tissue development and cancer progression.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7870680 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dynamic Expression of m6A Regulators During Multiple Human Tissue Development and Cancers.

Zhang Ya Y Xu Sicong S Xu Gang G Gao Yueying Y Li Si S Zhang Ke K Tian Zhanyu Z Guo Jing J Li Xia X Xu Juan J Li Yongsheng Y

Frontiers in cell and developmental biology 20210126

N6-methyladenosine (m6A) plays critical roles in human development and cancer progression. However, our knowledge regarding the dynamic expression of m6A regulators during human tissue development is still lacking. Here, we comprehensively analyzed the dynamic expression alterations of m6A regulators during seven tissue development and eight cancer types. We found that m6A regulators globally exhibited decreased expression during development. In additi ...[more]

PMID: 33575259

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Project description:BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely "writers," "erasers," and "readers." Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators' expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.

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Dynamic Expression of m⁶A Regulators During Multiple Human Tissue Development and Cancers.

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Dynamic Expression of m<sup>6</sup>A Regulators During Multiple Human Tissue Development and Cancers.

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