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Review
. 2024 Sep 4:15:1453774.
doi: 10.3389/fimmu.2024.1453774. eCollection 2024.

Regulatory effect of N6-methyladenosine on tumor angiogenesis

YuYan  1 , Enwu Yuan  1
Affiliations
Review

Regulatory effect of N6-methyladenosine on tumor angiogenesis

YuYan et al. Front Immunol. .

Abstract

Previous studies have demonstrated that genetic alterations governing epigenetic processes frequently drive tumor development and that modifications in RNA may contribute to these alterations. In the 1970s, researchers discovered that N6-methyladenosine (m6A) is the most prevalent form of RNA modification in advanced eukaryotic messenger RNA (mRNA) and noncoding RNA (ncRNA). This modification is involved in nearly all stages of the RNA life cycle. M6A modification is regulated by enzymes known as m6A methyltransferases (writers) and demethylases (erasers). Numerous studies have indicated that m6A modification can impact cancer progression by regulating cancer-related biological functions. Tumor angiogenesis, an important and unregulated process, plays a pivotal role in tumor initiation, growth, and metastasis. The interaction between m6A and ncRNAs is widely recognized as a significant factor in proliferation and angiogenesis. Therefore, this article provides a comprehensive review of the regulatory mechanisms underlying m6A RNA modifications and ncRNAs in tumor angiogenesis, as well as the latest advancements in molecular targeted therapy. The aim of this study is to offer novel insights for clinical tumor therapy.

Keywords: N6-methyladenosine; angiogenesis; anti-tumor therapy; noncoding RNA; regulatory role; tumor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Figures

Figure 1
Figure 1
Regulatory mechanism of m6A RNA methylation. M6A RNA methylation is a dynamic process that is governed primarily by three groups of proteins: “writers,” “erasers,” and “readers.” “Writers” and “erasers” are located predominantly in the nucleus, whereas some “readers,” such as HNRNPs and YTHDC1, also function in the nucleus. Other “readers,” including YTHDC2 and IGF2BP1/2/3, are found in both the cytoplasm and the nucleus, whereas “readers”, such as YTHDF1/2/3, are exclusively present in the cytoplasm. These three groups of proteins collaboratively regulate the output, stability, translation, and degradation of RNA.
Figure 2
Figure 2
Regulatory roles of m6A in tumor angiogenesis and development—direct and indirect mechanisms. The direct regulation of m6A involves METTLs, ALKBHs, YTHDFs, IGF2BPs, YTHDCs and FTO, which influence specific targets and cellular signaling pathways, thereby modulating tumor angiogenesis and cancer progression. Indirect regulation of m6A occurs through interactions between the three main components of its “life cycle” and ncRNAs (including miRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs)), collectively mediating tumor cell proliferation, migration, angiogenesis, and immune evasion. These mechanisms play crucial roles in various tumors, profoundly impacting tumor biology. In the figure, red indicates inhibitory effects, whereas black indicates promoting effects. (Created with MedPeer (www.medpeer.cn)).
Figure 3
Figure 3
Effective targets of m6A inhibitors in clinical oncology therapy. METTL3 can serve as a clinical inhibitory target for a range of cancers, including HNSCC, AML, GC, BC, CC, HCC, GBM, LC, CRC, and BCa. METTL14 can serve as a clinical inhibitory target for brain metastases of BC and CRC. ALKBH5 can serve as a clinical inhibitory target for CC in females and for GBM, PC, CRC, and brain metastases of BC. FTO can serve as a clinical inhibitory target for AML, GBM, CRC, and ICC. YTHDF2 can serve as a clinical inhibitory target for HCC and GC. YTHDF3 can serve as a clinical inhibitory target for brain metastases of BC and CRC. IGF2BP2 can serve as a clinical inhibitory target for LC, AML, and CRC. IGF2BP3 can serve as a clinical inhibitory target for CRC and GC. YTHDC2 can serve as a clinical inhibitory target for LC. (By Figdraw.).
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The key project of the Henan Provincial Medical Science and Technology Tackling Plan, jointly established by the province and the ministry, in 2023 (SBGJ202302081).

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