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m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review)

  • Authors:
    • Qian Yi
    • Yi Liao
    • Wei Sun
    • Jiachen Li
    • Dahang Yang
    • Hongxi Shang
    • Weichao Sun
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646099, P.R. China, Department of Technical Support, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Jiangsu 530021, P.R. China, Department of Orthopedics, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China
    Copyright: © Yi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 164
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    Published online on: August 5, 2025
       https://doi.org/10.3892/ijmm.2025.5605
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Abstract

N6‑methyladenosine (m6A) RNA modification represents a pivotal and novel post‑transcriptional modification in eukaryotic RNAs. Initially identified in messenger RNAs (mRNAs), m6A modification on these transcripts regulates a spectrum of essential cellular processes, including mRNA splicing, subcellular localization, stability and translation. Recent studies have highlighted the involvement of m6A methylation in both biological and pathological processes, particularly in cancer. Non‑coding RNAs (ncRNAs), a diverse class of RNA molecules that do not encode proteins, encompass microRNAs, long ncRNAs and circular RNAs. Notably, m6A has been recognized as a reversible epigenetic modification within ncRNAs, a discovery that has garnered considerable attention. This modification not only influences the stability of ncRNAs but also endows them with the novel capacity for peptide translation. The differential and specific expression pattern in diseases give these m6A‑modified ncRNAs potential as biomarkers for molecular diagnostics and targeted therapy, and using ncRNA‑encoded peptides as a target for immunotherapy has also been attempted. This review synthesizes the current understanding of m6A modifications in ncRNAs, explores the effects of m6A on ncRNA function and presents the latest insights into the role of ncRNA m6A modifications in disease progression. 
View Figures

Figure 1

Structural schematic representation
of the reversible and dynamic post-transcriptional m6A modification
of RNA. In the nucleus, methyltransferases and demethylases
regulate the m6A modifications of target mRNAs. m6A readers
modulate the splicing and transport of target mRNAs. In the
cytoplasm, different m6A readers control the stability,
degradation, localization and translation of mRNAs through distinct
mechanisms. WTAP, Wilms' tumor 1-associated protein; ZC3H13, zinc
finger CCCH-type containing 13; METTL3/14/16,
methyltransferase-like 3/14/16; VIRMA, vir like m6A
methyltransferase associated protein; FTO, fat mass and
obesity-associated protein; ALKBH5, α-ketoglutarate-dependent
dioxygenase alk B homolog 5; hnRNPC/hnRNPG/hnRNPA2B1, heterogeneous
nuclear ribonucleoprotein C/G/A2B1; IGF2BP1/2/3, insulin-like
growth factor 2 mRNA-binding protein 1/2/3; YTHDF1/2/3, YTHDC1/2,
YTH N6-methyladenosine RNA binding protein F1/2/3, C1/2.

Figure 2

Effects and functions of m6A
modification on ncRNAs (lncRNAs and circRNAs). (A) m6A modification
facilitates the biogenesis of ncRNAs. (B) m6A readers promote the
cytoplasmic export of ncRNAs. (C) m6A readers mediate the nuclear
retention or translocation of ncRNAs. (D) m6A readers regulate the
sorting of ncRNAs into exosomes. (E) m6A readers control the
stability or degradation of ncRNAs. (F) m6A-dependent translation
of ncRNAs. WTAP, Wilms' tumor 1-associated protein; lncRNA, long
noncoding RNA; METTL3/14, methyltransferase-like 3/14;
hnRNPC/hnRNPA2B1, heterogeneous nuclear ribonucleoprotein C/A2B1;
IGF2BP1/2/3, insulin-like growth factor 2 mRNA-binding protein
1/2/3; YTHDF1/2/3, YTH N6-methyladenosine RNA binding protein
F1/2/3, C1/2; eIF4Gs, eukaryotic translation initiation factor 4
gamma.

Figure 3

Effects of m6A-modified ncRNAs in the
pathological processes of cardiovascular diseases. (A) m6A-modified
ncRNAs facilitate the progression of atherosclerosis. (B) Role of
m6A-modified ncRNAs in regulating the viability of cardiomyocytes.
(C) m6A-modified ncRNAs facilitate the progression of myocardial
ischemia-reperfusion injury. WTAP, Wilms' tumor 1-associated
protein; METTL3/14, methyltransferase-like 3/14; YTHDF2/C1, YTH
N6-methyladenosine RNA binding protein F2/C1; hnRNP F,
heterogeneous nuclear ribonucleoprotein F; EIF4A3, eukaryotic
translation initiation factor 4A3; Sirt1, sirtuin 1; FOXO1,
forkhead box O1; NEAT1, nuclear paraspeckle assembly transcript 1;
FTO, fat mass and obesity-associated protein; KLF4, KLF
transcription factor 4; NLRP3, NLR family pyrin domain containing
3; RIPK1, receptor interacting serine/threonine kinase 1, ROS,
reactive oxygen species; DOX, doxorubicin; SNHG1/8, small nucleolar
RNA host gene 1/8; PTBP1, polypyrimidine tract binding protein 1;
ALAS2, 5′-aminolevulinate synthase 2; OPA1, OPA1 mitochondrial
dynamin like GTPase.

Figure 4

Effects of m6A-modified ncRNAs in the
pathological processes of metabolic diseases. (A) m6A-modified
ncRNAs facilitate the progression of gestational diabetes mellitus.
(B) Role of m6A-modified ncRNAs in regulating obesity. (C)
m6A-modified ncRNAs facilitate the progression of diabetic
cardiomyopathy. (D) m6A-modified ncRNAs facilitate the progression
of diabetic retinopathy. (E) m6A-modified ncRNAs facilitate the
progression of diabetic nephropathy. METTL3/14,
methyltransferase-like 3/14; lncRNA, long noncoding RNA; FOXO1,
forkhead box O1; XIST, X inactive specific transcript; BRG1, SBP
(S-ribonuclease binding protein) family protein; TINCR, TINCR
ubiquitin domain containing; NLRP3, NLR family pyrin domain
containing 3; SNHG7, small nucleolar RNA host gene 7; KHSRP,
KH-type splicing regulatory protein; MKL1, kinase MKL1 MAPK-like
protein; ALKBH5, α-ketoglutarate-dependent dioxygenase alk B
homolog 5; PTBP1, polypyrimidine tract binding protein 1; RAB3B,
member RAS oncogene family; GLUT4, solute carrier family 2
(facilitated glucose transporter), member 4; TUG1, taurine
up-regulated 1; LIN28B, lin-28 homolog B; MAPK1, mitogen-activated
protein kinase 1.

Figure 5

Effects of m6A-modified ncRNAs in the
pathological processes of neurological diseases. (A) m6A-modified
ncRNAs regulate the development and inflammation of the central
nervous system. (B) m6A-modified ncRNAs regulate the viability and
function of neuronal cells. (C) m6A-modified ncRNAs facilitate the
progression of cerebral ischemia-reperfusion injury. (D)
m6A-modified ncRNAs facilitate the progression of Alzheimer➢s
disease.
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Copy and paste a formatted citation
Spandidos Publications style
Yi Q, Liao Y, Sun W, Li J, Yang D, Shang H and Sun W: m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review). Int J Mol Med 56: 164, 2025.
APA
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., & Sun, W. (2025). m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review). International Journal of Molecular Medicine, 56, 164. https://doi.org/10.3892/ijmm.2025.5605
MLA
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., Sun, W."m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review)". International Journal of Molecular Medicine 56.4 (2025): 164.
Chicago
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., Sun, W."m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 164. https://doi.org/10.3892/ijmm.2025.5605
Copy and paste a formatted citation
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Spandidos Publications style
Yi Q, Liao Y, Sun W, Li J, Yang D, Shang H and Sun W: m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review). Int J Mol Med 56: 164, 2025.
APA
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., & Sun, W. (2025). m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review). International Journal of Molecular Medicine, 56, 164. https://doi.org/10.3892/ijmm.2025.5605
MLA
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., Sun, W."m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review)". International Journal of Molecular Medicine 56.4 (2025): 164.
Chicago
Yi, Q., Liao, Y., Sun, W., Li, J., Yang, D., Shang, H., Sun, W."m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 164. https://doi.org/10.3892/ijmm.2025.5605
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