PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells

Huang, Tianzhi; Yang, Yongyong; Song, Xian‐Rong; Wan, Xuechao; Wu, Bing‐Li; Sastry, Namratha; Horbinski, Craig; Zeng, Chang; Tiek, Deanna; Goenka, Anshika; Liu, Fabao; Brennan, Cameron; Kessler, John A.; Stupp, Roger; Nakano, ﻿Ichiro; Sulman, Erik P.; Nishikawa, Ryo; James, C. David; Zhang, Wei; Xu, Wei; Hu, Bo; Cheng, Shi‐Yuan

doi:10.1016/j.molcel.2021.01.015

Cited by 73 publications

(79 citation statements)

References 63 publications

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“…Furthermore, small molecule inhibitors of PRMT5 can drive GBM stem-like cells into senescence [ 113 ]. Recently, it was identified that protein arginine methyltransferase 6 (PRMT6) is required for methylation of regulator of chromatin condensation 1 ( RCC1 ) and further induce proliferation, stem-like properties and tumorigenicity of GBM stem cells (GSCs) [ 114 ]. Depletion of PRMT6 with a small molecule inhibitor could suppress RCC1 arginine methylation and improve the cytotoxic activity of radiotherapy against GSCs in vitro and in vivo.…”

Section: Targeting Epigenetic Alterationmentioning

confidence: 99%

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

Berglund

Etame

2021

IJMS

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Glioblastoma (GBM) is a highly lethal cancer that is universally refractory to the standard multimodal therapies of surgical resection, radiation, and chemotherapy treatment. Temozolomide (TMZ) is currently the best chemotherapy agent for GBM, but the durability of response is epigenetically dependent and often short-lived secondary to tumor resistance. Therapies that can provide synergy to chemoradiation are desperately needed in GBM. There is accumulating evidence that adaptive resistance evolution in GBM is facilitated through treatment-induced epigenetic modifications. Epigenetic alterations of DNA methylation, histone modifications, and chromatin remodeling have all been implicated as mechanisms that enhance accessibility for transcriptional activation of genes that play critical roles in GBM resistance and lethality. Hence, understanding and targeting epigenetic modifications associated with GBM resistance is of utmost priority. In this review, we summarize the latest updates on the impact of epigenetic modifications on adaptive resistance evolution in GBM to therapy.

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Section: Targeting Epigenetic Alterationmentioning

confidence: 99%

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

Berglund

Etame

2021

IJMS

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“…PRMT6 promotes the tumorigenicity and stem-like properties of the Glioblastoma stem cells (GSCs) by interacting with RCC1 and methylating it at Arg214. PRMT6-mediated methylation of RCC1 facilitates its association with chromatin and promotes mitosis through the generation of RAN-GTP [ 23 , 183 ].…”

Section: Role Of Prmt6 In Cancersmentioning

confidence: 99%

“…Depletion or knock-out of PRMT6 reduced (i) the cell proliferation and clonogenic capacity of the breast cancer cells [ 169 ], (ii) the cell migration and invasiveness of prostate cancer cells [ 172 ], (iii) endometrial cancer cell proliferation and migration [ 173 ], (iv) proliferation of lung adenocarcinoma cells [ 176 ] and (v) tumorigenic properties of gastric cancer cells [ 180 ]. It was reported that the inhibition of PRMT6 activity by the PRMT6 specific inhibitor EPZ020411 reduces the tumorigenicity of glioblastoma and improves its response to radiotherapy [ 23 ]. All these findings establish that PRMT6 is an important potential therapeutic target for various cancers.…”

Section: Role Of Prmt6 In Cancersmentioning

confidence: 99%

“…Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT which is involved in epigenetic regulation of gene expression [ 4 , 5 , 6 ], alternative splicing [ 7 , 8 ], development and differentiation [ 9 , 10 , 11 , 12 , 13 ], DNA repair [ 14 ], cell proliferation and senescence [ 15 , 16 , 17 , 18 , 19 , 20 ], DNA methylation [ 21 ], mitosis [ 22 , 23 ], inflammation [ 24 , 25 , 26 ], innate antiviral immunity [ 27 ], spermatogenesis [ 28 ], transactivation of nuclear receptors [ 7 , 29 , 30 ] and cell signaling [ 31 , 32 ]. A high throughput yeast two-hybrid screening of PRMT6 identified 36 proteins as potential interaction partners of PRMT6 suggesting the role of PRMT6 in various additional, so far unidentified cellular functions [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Structure, Activity and Function of the Protein Arginine Methyltransferase 6

Gupta

Kadumuri

Singh

et al. 2021

Life

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Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections.

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“…Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates protein substrates on arginine residues and has functions in epigenetic regulation of gene expression (18)(19)(20)(21), alternative splicing (13,22), development and differentiation (23)(24)(25), DNA repair (26), cell proliferation and senescence (27)(28)(29), DNA methylation (30), mitosis (31,32), inflammation (33)(34)(35), congenital antiviral immunity (36), spermatogenesis (37), transactivation of nuclear receptors (13,38) and cell signaling (39,40). In addition, the dysregulation of PRMT6 is also associated with viral diseases (41,42), cancer (43) and cardiac dystrophy (44).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of PRMT6 in Cancer

et al. 2022

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Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that is involved in epigenetic regulation of gene expression through methylating histone or non-histone proteins, and other processes such as alternative splicing, DNA repair, cell proliferation and senescence, and cell signaling. In addition, PRMT6 also plays different roles in various cancers via influencing cell growth, migration, invasion, apoptosis, and drug resistant, which make PRMT6 an anti-tumor therapeutic target for a variety of cancers. As a result, many PRMT6 inhibitors are being utilized to explore their efficacy as potential drugs for various cancers. In this review, we summarize the current knowledge on the function and structure of PRMT6. At the same time, we highlight the role of PRMT6 in different cancers, including the differentiation of its promotive or inhibitory effects and the underlying mechanisms. Apart from the above, current research progress and the potential mechanisms of PRMT6 behind them were also summarized.

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PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells

Cited by 73 publications

References 63 publications

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

Structure, Activity and Function of the Protein Arginine Methyltransferase 6

The Emerging Role of PRMT6 in Cancer

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