Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 9:14:1168365.
doi: 10.3389/fgene.2023.1168365. eCollection 2023.

Overview of distinct N6-Methyladenosine profiles of messenger RNA in osteoarthritis

Yang Yu  1 , Shitao Lu  1 , Yu Li  1 , Jianzhong Xu  1
Affiliations

Overview of distinct N6-Methyladenosine profiles of messenger RNA in osteoarthritis

Yang Yu et al. Front Genet. .

Abstract

Although N6-methyladenosine (m6A) modification is closely associated with the pathogenesis of osteoarthritis (OA), the mRNA profile of m6A modification in OA remains unknown. Therefore, our study aimed to identify common m6A features and novel m6A-related therapeutic targets in OA. In the present study, we identified 3962 differentially methylated genes (DMGs) and 2048 differentially expressed genes (DEGs) using methylated RNA immunoprecipitation next-generation sequencing (MeRIP-seq) and RNA-sequencing. A co-expression analysis of DMGs and DEGs showed that the expression of 805 genes was significantly affected by m6A methylation. Specifically, we obtained 28 hypermethylated and upregulated genes, 657 hypermethylated and downregulated genes, 102 hypomethylated and upregulated genes, and 18 hypomethylated and downregulated genes. The differential gene expression analysis based on GSE114007 revealed 2770 DEGs. The Weighted Gene Co-expression Network Analysis (WGCNA) based on GSE114007 identified 134 OA-related genes. By taking the intersection of these results, ten novel aberrantly expressed, m6A-modified and OA-related key genes were identified, including SKP2, SULF1, TNC, ZFP36, CEBPB, BHLHE41, SOX9, VEGFA, MKNK2 and TUBB4B. The present study may provide valuable insight into identifying m6A-related pharmacological targets in OA.

Keywords: WGCNA; m6A methylation; merip-seq; methylome profile; osteoarthritis.

PubMed Disclaimer

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
Flow chart of identification of m6A-related key genes and construction of a diagnostic model.
FIGURE 2
FIGURE 2
Transcriptome-wide analysis of m6A peaks. (A) Common motif enriched in the m6A peak in the mRNA identified in OA and normal cartilage. (B) The distribution of m6A peaks in the length of mRNA between OA and normal cartilage.
FIGURE 3
FIGURE 3
Statistics for genes with m6AI modifications in OA and normal cartilage. (A) Number of genes with m6A sites in OA and normal samples. (B) Number of genes with hyper- and hypomethylated m6A sites in OA.
FIGURE 4
FIGURE 4
Cluster analysis of m6A methylation in OA and normal knee cartilage. Heatmap of differentially methylated m6A peaks in 3962 DMGs.
FIGURE 5
FIGURE 5
GO functional enrichment analysis and KEGG pathway analysis of DMGs. (A) Biological process annotation diagram (Top10). (B) Cellular component annotation diagram (Top10). (C) Molecular function annotation diagram (Top10). (D) KEGG annotation.
FIGURE 6
FIGURE 6
The association analysis between DEGs and DMGs. 805 genes were identified, including 28 hypermethylated and upregulated genes, 657 hypermethylated and downregulated genes, 102 hypomethylated and upregulated genes, and 18 hypomethylated and downregulated genes. Genes with the top 10 m6A modification sites were annotated.
FIGURE 7
FIGURE 7
WGCNA analysis. (A) Identification of optimal soft threshold power for the co-expression network. (B) Clustering dendrogram of genes. (C) Module-trait relationships.
FIGURE 8
FIGURE 8
Venn diagram of the WGCNA, DEGs and DMGs. Ten m6A-modified key genes were identified by crossover.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bechara R., Amatya N., Bailey R. D., Li Y., Aggor F. E. Y., Li D. D., et al. (2021). The m(6)A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis. Sci. Immunol. 6 (61), eabd1287. 10.1126/sciimmunol.abd1287 - DOI - PMC - PubMed
    1. Cai Z., Moten A., Peng D., Hsu C. C., Pan B. S., Manne R., et al. (2020). The Skp2 pathway: A critical target for cancer therapy. Semin. Cancer Biol. 67 (2), 16–33. 10.1016/j.semcancer.2020.01.013 - DOI - PMC - PubMed
    1. Chen X., Gong W., Shao X., Shi T., Zhang L., Dong J., et al. (2022). METTL3-mediated m(6)A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Ann. Rheum. Dis. 81 (1), 87–99. 10.1136/annrheumdis-2021-221091 - DOI - PubMed
    1. Chevalier X., Groult N., Larget-Piet B., Zardi L., Hornebeck W. (1994). Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 37 (7), 1013–1022. 10.1002/art.1780370706 - DOI - PubMed
    1. Chiquet M., Fambrough D. M. (1984). Chick myotendinous antigen. II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. J. Cell Biol. 98 (6), 1937–1946. 10.1083/jcb.98.6.1937 - DOI - PMC - PubMed

Grants and funding

This study was supported by funds from the Youth Foundation of the First Affiliated Hospital of Zhengzhou University (YNQN-70131).