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
Review
. 2022 Apr 28;7(1):142.
doi: 10.1038/s41392-022-01003-0.

Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine

Chen Xue #  1 , Qingfei Chu #  1 , Qiuxian Zheng #  1 , Shiman Jiang  1 , Zhengyi Bao  1 , Yuanshuai Su  1 , Juan Lu  2 , Lanjuan Li  3
Affiliations
Review

Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine

Chen Xue et al. Signal Transduct Target Ther. .

Abstract

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes. Epigenetic modifications regulate many biological processes, such as growth, aging, and various diseases, including cancer. With the advancement of next-generation sequencing technology, the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific research. This review studied several common RNA modifications, such as N6-methyladenosine, 5-methylcytosine, and pseudouridine. The deposition and roles of these modifications in coding and noncoding RNAs are summarized in detail. Based on the RNA modification background, this review summarized the expression, function, and underlying molecular mechanism of these modifications and their regulators in cancer and further discussed the role of some existing small-molecule inhibitors. More in-depth studies on RNA modification and cancer are needed to broaden the understanding of epigenetics and cancer diagnosis, treatment, and prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Deregulation of m6A, m5C, and Ψ regulators in human cancers. Red mains an oncogenic role, while green mains a tumor suppressive role. BLC bladder cancer; HCC hepatocellular carcinoma; CC cervical cancer; GBC gallbladder carcinoma; AML acute myeloid leukemia; CRC colorectal cancer; PC pancreatic cancer; GC gastric cancer; GBM glioblastoma; PCa prostate cancer; BRC breast cancer; OC ovarian cancer; ESCC esophageal squamous cell carcinoma; NSCLC non-small cell lung cancer; LUAD Lung adenocarcinoma; LUSC lung squamous cell carcinoma; OS osteosarcoma; RCC renal cell carcinoma; EC esophageal cancer. Image created with BioRender (https://biorender.com/)
Fig. 2
Fig. 2
The most common types of RNA modifications and the mechanism of m6A regulation. Image created with BioRender (https://biorender.com/)
Fig. 3
Fig. 3
The role of m6A in digestive system neoplasms. m6A can not only promote cancer progression, but it also plays a role in inhibiting progression. This figure mainly proposes how writers, erasers, and readers participate in the regulation of various genes and pathways in cancer progression. ESCC esophageal squamous cell carcinoma; GC gastric cancer; HB hepatoblastoma; CRC colorectal cancer; HCC hepatocellular carcinoma; PC pancreatic cancer. Image created with BioRender (https://biorender.com/)
Fig. 4
Fig. 4
The mechanism of m5C regulation and the common detection methods. Image created with BioRender (https://biorender.com/)
Fig. 5
Fig. 5
The mechanism of Ψ regulation. There are two main ways of pseudouracilylation of RNA substrates in eukaryotes. One is an RNA-independent mechanism whereby PUSs directly recognize and catalyze substrates. The other is an RNA-dependent mechanism that requires catalysis by box H/ACA RNPs. Each RNP contains a unique guide RNA component and a set of evolutionarily conserved four core proteins. Among them, only DCK1 has catalytic activity. Nhp2, Nop10, and Gar1 are regulatory units. Image created with BioRender (https://biorender.com/)
See this image and copyright information in PMC

References

    1. Sun H, Wang X, Zhai S. The rational design and biological mechanisms of nanoradiosensitizers. Nanomaterials. 2020;10:504. doi: 10.3390/nano10030504. - DOI - PMC - PubMed
    1. Hu SC, Yang J, Chen C, Song JR, Pan WD. Design, synthesis of novel tetrandrine-14-l-amino acid and tetrandrine-14-l-amino acid-urea derivatives as potential anti-cancer agents. Molecules. 2020;25:1738. doi: 10.3390/molecules25071738. - DOI - PMC - PubMed
    1. Zeng D, et al. Synergistic photothermal/photodynamic suppression of prostatic carcinoma by targeted biodegradable MnO(2) nanosheets. Drug Deliv. 2019;26:661–672. doi: 10.1080/10717544.2019.1631409. - DOI - PMC - PubMed
    1. Rong Y, et al. DDRS: Detection of drug response SNPs specifically in patients receiving drug treatment. Comput. Struct. Biotechnol. J. 2021;19:3650–3657. doi: 10.1016/j.csbj.2021.06.026. - DOI - PMC - PubMed
    1. Chen MH, et al. How may ramucirumab help improve treatment outcome for patients with gastrointestinal cancers? Cancers. 2021;13:3536. doi: 10.3390/cancers13143536. - DOI - PMC - PubMed

Publication types