A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer

Tang, Stephen; Sethunath, Vidyalakshmi; Metaferia, Nebiyou Y.; Nogueira, Marina F.; Gallant, Daniel S; Garner, Emma R.; Lairson, Lauren A.; Penney, Christopher M; Li, Jiao; Gelbard, Maya K.; Alaiwi, Sarah Abou; Seo, Ji-Heui; Hwang, Justin; Strathdee, Craig A.; Baca, Sylvan C.; AbuHammad, Shatha; Zhang, Xiaoyang; Doench, John G.; Hahn, William C.; Takeda, David Y.; Freedman, Matthew L.; Choi, Peter S.; Viswanathan, Srinivas R.

doi:10.1016/j.celrep.2022.110417

Cited by 23 publications

(10 citation statements)

References 84 publications

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“…PRMT1 highly expresses in metastatic prostate cancer and high PRMT1 expression shows low survival rates. 105 In particular, PRMT4 is highly expressed in hormone-naïve high-grade prostate cancer patients (prognostic grade group 3–5) and correlated with markers of cell cycle regulation, and both PRMT1 and PRMT4 are correlated with markers of epithelial-to-mesenchymal transition. 106 Recently, pheophorbide a/b isolated from Foeniculum vulgare was identified as an inhibitor of PRMT4 and PRMT5, suppressing prostate cancer cell proliferation.…”

Section: The Role Of Arginine Methyltransferases In Prostate Cancermentioning

confidence: 99%

Recent advances in prostate cancer: WNT signaling, chromatin regulation, and transcriptional coregulators

Takahashi

Takada

2023

Asian Journal of Andrology

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Prostate cancer is one of the most common diseases in men worldwide. Surgery, radiation therapy, and hormonal therapy are effective treatments for early-stage prostate cancer. However, the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer. To develop novel drugs for castration-resistant prostate cancer, the molecular mechanisms of prostate cancer progression must be elucidated. Among the signaling pathways regulating prostate cancer development, recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family (WNT) signaling pathways, mainly that involving WNT5A, in prostate cancer progression and metastasis; however, its role remains controversial. Moreover, chromatin remodelers such as the switch/sucrose nonfermentable (SWI/SNF) complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes. Here, we review the roles of noncanonical WNT signaling pathways, chromatin remodelers, and epigenetic enzymes in the development and progression of prostate cancer.

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Section: The Role Of Arginine Methyltransferases In Prostate Cancermentioning

confidence: 99%

Recent advances in prostate cancer: WNT signaling, chromatin regulation, and transcriptional coregulators

Takahashi

Takada

2023

Asian Journal of Andrology

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“…A genome-scale CRISPR screen identified PRMT1 as a key mediator in the androgen receptor (AR) signaling pathway. Interestingly, it was found that PRMT1 could regulate the activity of AR enhancers, controlling the transcription and expression of the AR gene [ 100 ]. Targeting PRMT1 reduces the H4R3me2a modification at the AR locus, inhibiting AR-FL and AR-V7 transcription [ 101 ].…”

Section: Prostate Cancermentioning

confidence: 99%

PRMT1 in human neoplasm: cancer biology and potential therapeutic target

Shen,

Zhou,

Xiao

et al. 2024

Cell Commun Signal

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Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein arginine methyltransferase, plays a crucial role in normal biological functions by catalyzing the methylation of arginine side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression and the initiation and progression of tumors, significantly impacting patient prognosis, attributed to PRMT1’s involvement in regulating various facets of tumor cell biology, including DNA damage repair, transcriptional and translational regulation, as well as signal transduction. In this review, we present an overview of recent advancements in PRMT1 research across different tumor types, with a specific focus on its contributions to tumor cell proliferation, metastasis, invasion, and drug resistance. Additionally, we expound on the dynamic functions of PRMT1 during distinct stages of cancer progression, elucidating its unique regulatory mechanisms within the same signaling pathway and distinguishing between its promotive and inhibitory effects. Importantly, we sought to provide a comprehensive summary and analysis of recent research progress on PRMT1 in tumors, contributing to a deeper understanding of its role in tumorigenesis, development, and potential treatment strategies.

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“…Multiple small molecule inhibitors of PRMT1 have been developed, the first of which has entered clinical trials for a number of tumor types (NCT03666988) [ 259 ]. PRMT1 expression is upregulated in advanced PCa and it has been identified as a regulator of AR-V7 in a whole-genome CRISPR screen [ 268 , 269 ]. The depletion of PRMT1 reduces the occupancy of AR at its target genes, an effect that has also been observed following treatment with the metabolite spermine, which has been shown to inhibit PRMT1 [ 269 , 270 ].…”

Section: Emerging Targets In Crpcmentioning

confidence: 99%

Exploiting the DNA Damage Response for Prostate Cancer Therapy

Stracker,

Osagie,

Escorcia

et al. 2023

Cancers

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Prostate cancers that progress despite androgen deprivation develop into castration-resistant prostate cancer, a fatal disease with few treatment options. In this review, we discuss the current understanding of prostate cancer subtypes and alterations in the DNA damage response (DDR) that can predispose to the development of prostate cancer and affect its progression. We identify barriers to conventional treatments, such as radiotherapy, and discuss the development of new therapies, many of which target the DDR or take advantage of recurring genetic alterations in the DDR. We place this in the context of advances in understanding the genetic variation and immune landscape of CRPC that could help guide their use in future treatment strategies. Finally, we discuss several new and emerging agents that may advance the treatment of lethal disease, highlighting selected clinical trials.

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A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer

Cited by 23 publications

References 84 publications

Recent advances in prostate cancer: WNT signaling, chromatin regulation, and transcriptional coregulators

Recent advances in prostate cancer: WNT signaling, chromatin regulation, and transcriptional coregulators

PRMT1 in human neoplasm: cancer biology and potential therapeutic target

Exploiting the DNA Damage Response for Prostate Cancer Therapy

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