The Emerging Role of CARM1 in Cancer

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2024 Apr 15

PMID 38619752

Authors

Zizhuo Xie

Yuan Tian

Xiaohan Guo

Na Xie

Affiliations

Soon will be listed here.

Abstract

Coactivator-associated arginine methyltransferase 1 (CARM1), pivotal for catalyzing arginine methylation of histone and non-histone proteins, plays a crucial role in developing various cancers. CARM1 was initially recognized as a transcriptional coregulator by orchestrating chromatin remodeling, transcription regulation, mRNA splicing and stability. This diverse functionality contributes to the recruitment of transcription factors that foster malignancies. Going beyond its established involvement in transcriptional control, CARM1-mediated methylation influences a spectrum of biological processes, including the cell cycle, metabolism, autophagy, redox homeostasis, and inflammation. By manipulating these physiological functions, CARM1 becomes essential in critical processes such as tumorigenesis, metastasis, and therapeutic resistance. Consequently, it emerges as a viable target for therapeutic intervention and a possible biomarker for medication response in specific cancer types. This review provides a comprehensive exploration of the various physiological functions of CARM1 in the context of cancer. Furthermore, we discuss potential CARM1-targeting pharmaceutical interventions for cancer therapy.

References

Espinosa L, Cathelin S, DAltri T, Trimarchi T, Statnikov A, Guiu J . The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia. Cancer Cell. 2010; 18(3):268-81. PMC: 2963042. DOI: 10.1016/j.ccr.2010.08.006. View

An W, Kim J, Roeder R . Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell. 2004; 117(6):735-48. DOI: 10.1016/j.cell.2004.05.009. View

Lim C, Alkon D . Protein kinase C stimulates HuD-mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture. Hippocampus. 2012; 22(12):2303-19. DOI: 10.1002/hipo.22048. View

Hong H, Kao C, Jeng M, Eble J, Koch M, Gardner T . Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer. 2004; 101(1):83-9. DOI: 10.1002/cncr.20327. View

Greenblatt S, Man N, Hamard P, Asai T, Karl D, Martinez C . CARM1 Is Essential for Myeloid Leukemogenesis but Dispensable for Normal Hematopoiesis. Cancer Cell. 2018; 33(6):1111-1127.e5. PMC: 6191185. DOI: 10.1016/j.ccell.2018.05.007. View

Zika E, Fauquier L, Vandel L, Ting J . Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN-gamma-inducible MHC-II gene expression. Proc Natl Acad Sci U S A. 2005; 102(45):16321-6. PMC: 1283426. DOI: 10.1073/pnas.0505045102. View

Kim E, Liu P, Zhang S, Donahue K, Wang Y, Schehr J . BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity. Nucleic Acids Res. 2021; 49(21):12211-12233. PMC: 8643633. DOI: 10.1093/nar/gkab1122. View

Bertozzi S, Londero A, Viola L, Orsaria M, Bulfoni M, Marzinotto S . TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study. BMC Cancer. 2021; 21(1):1118. PMC: 8524961. DOI: 10.1186/s12885-021-08844-y. View

Charoensuksai P, Kuhn P, Wang L, Sherer N, Xu W . O-GlcNAcylation of co-activator-associated arginine methyltransferase 1 regulates its protein substrate specificity. Biochem J. 2015; 466(3):587-99. DOI: 10.1042/BJ20141072. View

10.

Jin W, Zhang J, Chen X, Yin S, Yu H, Gao F . Unraveling the complexity of histone-arginine methyltransferase CARM1 in cancer: From underlying mechanisms to targeted therapeutics. Biochim Biophys Acta Rev Cancer. 2023; 1878(4):188916. DOI: 10.1016/j.bbcan.2023.188916. View

11.

Paquette M, El-Houjeiri L, Zirden L, Puustinen P, Blanchette P, Jeong H . AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3. Autophagy. 2021; 17(12):3957-3975. PMC: 8726606. DOI: 10.1080/15548627.2021.1898748. View

12.

Yang G, Zhou C, Wang R, Huang S, Wei Y, Yang X . Base-Editing-Mediated R17H Substitution in Histone H3 Reveals Methylation-Dependent Regulation of Yap Signaling and Early Mouse Embryo Development. Cell Rep. 2019; 26(2):302-312.e4. DOI: 10.1016/j.celrep.2018.12.046. View

13.

Li X, Lai Y, Li J, Zou M, Zou C . Oxidative stress destabilizes protein arginine methyltransferase 4 via glycogen synthase kinase 3β to impede lung epithelial cell migration. Am J Physiol Cell Physiol. 2017; 313(3):C285-C294. PMC: 5625095. DOI: 10.1152/ajpcell.00073.2017. View

14.

Kim K, Wang D, Campbell M, Huerta S, Shevchenko B, Izumiya C . PRMT4-mediated arginine methylation negatively regulates retinoblastoma tumor suppressor protein and promotes E2F-1 dissociation. Mol Cell Biol. 2014; 35(1):238-48. PMC: 4295381. DOI: 10.1128/MCB.00945-14. View

15.

Karakashev S, Zhu H, Wu S, Yokoyama Y, Bitler B, Park P . CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity. Nat Commun. 2018; 9(1):631. PMC: 5809368. DOI: 10.1038/s41467-018-03031-3. View

16.

Bang J, Lee E, Lee A, Il Lee J, Choi S, Seol D . The effect of cell penetrating peptide-conjugated coactivator-associated arginine methyltransferase 1 (CPP-CARM1) on the cloned mouse embryonic development. Sci Rep. 2018; 8(1):16721. PMC: 6233168. DOI: 10.1038/s41598-018-35077-0. View

17.

Frietze S, Lupien M, Silver P, Brown M . CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1. Cancer Res. 2008; 68(1):301-6. DOI: 10.1158/0008-5472.CAN-07-1983. View

18.

Chen D, Ma H, Hong H, Koh S, Huang S, Schurter B . Regulation of transcription by a protein methyltransferase. Science. 1999; 284(5423):2174-7. DOI: 10.1126/science.284.5423.2174. View

19.

Cheng D, Cote J, Shaaban S, Bedford M . The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol Cell. 2007; 25(1):71-83. DOI: 10.1016/j.molcel.2006.11.019. View

20.

Tewary S, Zheng Y, Ho M . Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level. Cell Mol Life Sci. 2019; 76(15):2917-2932. PMC: 6741777. DOI: 10.1007/s00018-019-03145-x. View