YT521-B Homology Domain Family Proteins As N6-methyladenosine Readers in Tumors

Overview

Journal Front Genet

Date 2022 Aug 26

PMID 36017491

Authors

Heng Yang

Chengyao Chiang

Qinhong Luo

ChunLan Chen

JunRong Huang

Lizhi Zhu

Duo Zheng

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (m6A) is the most abundant internal chemical modification of eukaryotic mRNA and plays diverse roles in gene regulation. The m6A modification plays a significant role in numerous cancer types, including kidney, stomach, lung, bladder tumors, and melanoma, through varied mechanisms. As direct m6A readers, the YT521-B homology domain family proteins (YTHDFs) play a key role in tumor transcription, translation, protein synthesis, tumor stemness, epithelial-mesenchymal transition (EMT), immune escape, and chemotherapy resistance. An in-depth understanding of the molecular mechanism of YTHDFs is expected to provide new strategies for tumor treatment. In this review, we provide a systematic description of YTHDF protein structure and its function in tumor progression.

Citing Articles

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PMID: 38811341 PMC: 11309927. DOI: 10.1111/cas.16228.

References

Liao S, Sun H, Xu C . YTH Domain: A Family of N-methyladenosine (mA) Readers. Genomics Proteomics Bioinformatics. 2018; 16(2):99-107. PMC: 6112328. DOI: 10.1016/j.gpb.2018.04.002. View

Ma C, Liao S, Zhu Z . Crystal structure of human YTHDC2 YTH domain. Biochem Biophys Res Commun. 2019; 518(4):678-684. DOI: 10.1016/j.bbrc.2019.08.107. View

Helm M, Motorin Y . Detecting RNA modifications in the epitranscriptome: predict and validate. Nat Rev Genet. 2017; 18(5):275-291. DOI: 10.1038/nrg.2016.169. View

Hao L, Wang J, Liu B, Yan J, Li C, Jiang J . m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. Biochim Biophys Acta Mol Cell Res. 2020; 1868(1):118878. DOI: 10.1016/j.bbamcr.2020.118878. View

Zheng B, Wang J, Zhao G, Chen X, Yao Z, Niu Z . A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder. Biosci Rep. 2021; 41(4). PMC: 8035626. DOI: 10.1042/BSR20204456. View

Dai D, Wang H, Zhu L, Jin H, Wang X . N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis. 2018; 9(2):124. PMC: 5833385. DOI: 10.1038/s41419-017-0129-x. View

Xu C, Liu K, Ahmed H, Loppnau P, Schapira M, Min J . Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins. J Biol Chem. 2015; 290(41):24902-13. PMC: 4598999. DOI: 10.1074/jbc.M115.680389. View

Zhang C, Huang S, Zhuang H, Ruan S, Zhou Z, Huang K . YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation. Oncogene. 2020; 39(23):4507-4518. DOI: 10.1038/s41388-020-1303-7. View

Pak O, Zaitsev S, Shevchenko V, Sharma A, Sharma H, Bryukhovetskiy I . Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation. Prog Brain Res. 2021; 266:195-209. DOI: 10.1016/bs.pbr.2021.06.010. View

10.

Li A, Chen Y, Ping X, Yang X, Xiao W, Yang Y . Cytoplasmic mA reader YTHDF3 promotes mRNA translation. Cell Res. 2017; 27(3):444-447. PMC: 5339832. DOI: 10.1038/cr.2017.10. View

11.

Zhang Y, Li L, Ye Z, Zhang L, Yao N, Gai L . Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma. Ann Transl Med. 2021; 9(20):1554. PMC: 8576668. DOI: 10.21037/atm-21-4712. View

12.

Yarchoan M, Johnson 3rd B, Lutz E, Laheru D, Jaffee E . Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017; 17(4):209-222. PMC: 5575801. DOI: 10.1038/nrc.2016.154. View

13.

Tsuchiya K, Yoshimura K, Inoue Y, Iwashita Y, Yamada H, Kawase A . YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer. Oncoimmunology. 2021; 10(1):1962656. PMC: 8366544. DOI: 10.1080/2162402X.2021.1962656. View

14.

Li Y, Bedi R, Moroz-Omori E, Caflisch A . Structural and Dynamic Insights into Redundant Function of YTHDF Proteins. J Chem Inf Model. 2020; 60(12):5932-5935. DOI: 10.1021/acs.jcim.0c01029. View

15.

Huang G, Wang M, Li X, Wu J, Chen S, Du N . TUSC7 suppression of Notch activation through sponging MiR-146 recapitulated the asymmetric cell division in lung adenocarcinoma stem cells. Life Sci. 2019; 232:116630. DOI: 10.1016/j.lfs.2019.116630. View

16.

Chen J, Solomides C, Simpkins F, Simpkins H . The role of Nrf2 and ATF2 in resistance to platinum-based chemotherapy. Cancer Chemother Pharmacol. 2017; 79(2):369-380. DOI: 10.1007/s00280-016-3225-1. View

17.

Gilbert W, Bell T, Schaening C . Messenger RNA modifications: Form, distribution, and function. Science. 2016; 352(6292):1408-12. PMC: 5094196. DOI: 10.1126/science.aad8711. View

18.

Laudato S, Patil N, Abba M, Leupold J, Benner A, Gaiser T . P53-induced miR-30e-5p inhibits colorectal cancer invasion and metastasis by targeting ITGA6 and ITGB1. Int J Cancer. 2017; 141(9):1879-1890. DOI: 10.1002/ijc.30854. View

19.

Pan H, Pan Z, Guo F, Meng F, Zu L, Fan Y . MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer. BMC Cancer. 2021; 21(1):1218. PMC: 8590782. DOI: 10.1186/s12885-021-08961-8. View

20.

Yang S, Wei J, Cui Y, Park G, Shah P, Deng Y . mA mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun. 2019; 10(1):2782. PMC: 6592937. DOI: 10.1038/s41467-019-10669-0. View