Research progress on PRMTs involved in epigenetic modification and tumour signalling pathway regulation (Review)

Abstract

Posttranslational modification (PTM) of proteins is essential for increasing protein diversity and maintaining cellular homeostasis, but uncontrolled modification may lead to tumorigenesis. Arginine methylation is a tumorigenesis-related PTM that affects protein function through protein-protein and protein-nucleic acid interactions. Protein arginine methyltransferases (PRMTs) have vital roles in signalling pathways of tumour-intrinsic and tumour-extrinsic microenvironments. The present review summarizes the modifications and functions of PRMTs in histone methylation and nonhistone methylation, their roles in RNA splicing and DNA damage repair and the currently known functions in tumour metabolism and immunotherapy. In conclusion, this article reviews the latest research progress on the role of PRMTs in tumour signal transduction, providing a theoretical basis for clinical diagnosis and treatment. Targeting PRMTs is expected to provide new directions for tumour therapy.

Ellagic acid: a potential inhibitor of enhancer of zeste homolog-2 and protein arginine methyltransferase-5

“…It has been reported in vivo model that role of EZH2 and PRMT5 in synthetic small molecules reduced the tumor size as well as recover from the cancers (10,11,14) In the present study upon treatment with EA in Table1: Interaction profiles of EA with human EZH2 and PRMT5: MEP50: were analyzed using several protein complexes, specifically 5HYN and 4MI5 for EZH2 and 4X60, 4X61, 4X63 for PRMT5: Molecular docking studies were conducted with these complexes. Additionally, the GlideXP docking scores of EA with Sfg, SAM, and SAH were evaluated and are included.…”

Epigallocatechin-3-gallate inhibit the protein arginine methyltransferase 5 and Enhancer of Zeste homolog 2 in breast cancer bothin vitroandin vivo

“…The EZH1, and EZH2 are two well-known methyltransferases among KMTs. The PRMTs, include type I, II and III (5).…”

“…The EZH1, and EZH2 are two well-known methyltransferases among KMTs. The PRMTs, include type I, II and III (5) . Type I PRMTs forms the asymmetric dimethylation of arginine residues that include PRMT1,2,3,4,6,8 whereas type II PRMT5/7 adds the methyl groups to arginine side chain symmetrically while type III only produces monomethylated arginine (7) .…”

“…The PRMT5-MEP50 complex consists of four PRMT5 and MEP50 molecules this association very critical for optimal activity (10)(11) . The role of PRMT5 has been well established in tumorigenesis, RNA metabolism, transcriptional regulation, DNA repair, signal transduction and ribosome biogenesis (5,10). According to various studies reported, PRMT5 is involved in a multitude of cellular processes, exerting its influence through the methylation of a diverse array of both cytoplasmic and nuclear substrates.…”

“…The PRMT5-mediated methylation of protein/s is implicated in the control of normal and pathological status, in maintenance of tissue homeostasis, development, survival and self-renewing capacity of stem/progenitor cells in hematopoietic, nervous, muscular, and reproductive systems. Apart from that PRMT5 is upregulated in several human cancers, including breast cancer, lung cancer, prostate cancer, lymphomas and colorectal cancer (5,6,10), its overexpression observed in autoimmune diseases (12), inflammation diseases (13) as well. The mechanism of upregulation of PRMT5 in disease status is still unknown.…”