keyword
MENU ▼
Read by QxMD icon Read
search

Prmt5 cancer

keyword
https://www.readbyqxmd.com/read/29262329/prmt5-is-a-critical-regulator-of-breast-cancer-stem-cell-function-via-histone-methylation-and-foxp1-expression
#1
Kelly Chiang, Agnieszka E Zielinska, Abeer M Shaaban, Maria Pilar Sanchez-Bailon, James Jarrold, Thomas L Clarke, Jingxian Zhang, Adele Francis, Louise J Jones, Sally Smith, Olena Barbash, Ernesto Guccione, Gillian Farnie, Matthew J Smalley, Clare C Davies
Breast cancer progression, treatment resistance, and relapse are thought to originate from a small population of tumor cells, breast cancer stem cells (BCSCs). Identification of factors critical for BCSC function is therefore vital for the development of therapies. Here, we identify the arginine methyltransferase PRMT5 as a key in vitro and in vivo regulator of BCSC proliferation and self-renewal and establish FOXP1, a winged helix/forkhead transcription factor, as a critical effector of PRMT5-induced BCSC function...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29250158/function-of-mir-25-in-the-invasion-and-metastasis-of-esophageal-squamous-carcinoma-cells-and-bioinformatical-analysis-of-the-mir-106b-25-cluster
#2
Meng Wang, Yangyang Ou Yang, Qingtao Jin, Linlin Shang, Jian Zhang
MicroRNAs (miRNAs/miRs) are a class of small, non-coding RNA molecules that serve a key function in carcinogenesis and tumor progression. Recent evidence indicates that miRNAs may act as powerful regulators of migration and invasion. The present study aimed to investigate the effect of miR-25 on the invasion and metastasis of KYSE-150 and EC109 esophageal squamous cell carcinoma (ESCC) cells, and predict the mechanism of this effect by bioinformatically analyzing the miR-106b-25 cluster. In order to alter the expression of miR-25 in the two cell lines, a miR-25 inhibitor or mimic were transfected into the cells, which were then studied via Transwell migration and invasion assays...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29227283/sharpin-mediated-regulation-of-protein-arginine-methyltransferase-5-controls-melanoma-growth
#3
Hironari Tamiya, Hyungsoo Kim, Oleksiy Klymenko, Heejung Kim, Yongmei Feng, Tongwu Zhang, Ji Yun Han, Ayako Murao, Scott J Snipas, Lucia Jilaveanu, Kevin Brown, Harriet Kluger, Hao Zhang, Kazuhiro Iwai, Ze'ev A Ronai
SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC), plays important roles in NF-κB signaling and inflammation. Here, we have demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth. We observed that SHARPIN interacted with PRMT5, a type II protein arginine methyltransferase, and increased its multiprotein complex and methyltransferase activity. Activated PRMT5 controlled the expression of the transcription factors SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the transcriptional corepressor SKI...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29185119/prmt5-determines-the-sensitivity-to-chemotherapeutics-by-governing-stemness-in-breast-cancer
#4
Zhe Wang, Jing Kong, Ying Wu, Juliang Zhang, Ting Wang, Nanlin Li, Jing Fan, Hui Wang, Jian Zhang, Rui Ling
PURPOSE: Acquired resistance to chemotherapeutic agents in breast cancer is a major clinical challenge. Recent studies have shown that the emergence of cancer stem cells contributes to the development of drug resistance, and the protein arginine methyltransferase 5 (PRMT5) was crucial for the maintenance of stemness. However, the roles of PRMT5 in breast cancer cell stemness and the development of cancer drug resistance have not been clarified. In this study, we investigated the effect of PRMT5 on the sensitivity to doxorubicin and cell stemness in breast cancer...
November 28, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29099132/development-of-an-alphalisa-high-throughput-technique-to-screen-for-small-molecule-inhibitors-targeting-protein-arginine-methyltransferases
#5
Lakshmi Prabhu, Lan Chen, Han Wei, Özlem Demir, Ahmad Safa, Lifan Zeng, Rommie E Amaro, Bert H O'Neil, Zhon-Yin Zhang, Tao Lu
The protein arginine methyltransferase (PRMT) family of enzymes comprises nine family members in mammals. They catalyze arginine methylation, either monomethylation or symmetric/asymmetric dimethylation of histone and non-histone proteins. PRMT methylation of its substrate proteins modulates cellular processes such as signal transduction, transcription, and mRNA splicing. Recent studies have linked overexpression of PRMT5, a member of the PRMT superfamily, to oncogenesis, making it a potential target for cancer therapy...
November 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29076773/targeting-protein-arginine-methyltransferase-5-in-disease
#6
André Richters
PRMT5 catalyzes the mono- and symmetric dimethylation of the arginine N-guanidine group of a wide variety of target proteins including histones, transcriptional elongation factors, kinases and tumor suppressors by utilizing the essential co-factor S-adenosylmethionine as methyl source. PRMT5 overexpression has been linked to the progression of various diseases, including cancer, and is oftentimes associated with a poor prognosis. Therefore, PRMT5 is promoted as a valuable target for drug discovery approaches and was a subject matter in recent endeavors aiming for the development of specific PRMT5 inhibitors...
October 27, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29017049/exploiting-the-hidden-treasure-of-detained-introns
#7
Xiang-Dong Fu
Many mammalian genes contain poorly spliced introns, resulting in nuclear detention of partially spliced transcripts, which may be exploited to modulate gene expression. In this issue of Cancer Cell, Braun et al. report that the arginine methyltransferase PRMT5 is critical for tumor cell proliferation by regulating numerous detained introns.
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28987382/arginine-methyltransferase-inhibitor-1-inhibits-gastric-cancer-by-downregulating-eif4e-and-targeting-prmt5
#8
Baolai Zhang, Su Zhang, Lijuan Zhu, Xue Chen, Yunfeng Zhao, Li Chao, Juanping Zhou, Xing Wang, Xinyang Zhang, Nengqian Ma
Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s)...
October 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28977470/the-prmt5-wdr77-complex-regulates-alternative-splicing-through-znf326-in-breast-cancer
#9
Madhumitha Rengasamy, Fan Zhang, Ajay Vashisht, Won-Min Song, Francesca Aguilo, Yifei Sun, SiDe Li, Weijia Zhang, Bin Zhang, James A Wohlschlegel, Martin J Walsh
We observed overexpression and increased intra-nuclear accumulation of the PRMT5/WDR77 in breast cancer cell lines relative to immortalized breast epithelial cells. Utilizing mass spectrometry and biochemistry approaches we identified the Zn-finger protein ZNF326, as a novel interaction partner and substrate of the nuclear PRMT5/WDR77 complex. ZNF326 is symmetrically dimethylated at arginine 175 (R175) and this modification is lost in a PRMT5 and WDR77-dependent manner. Loss of PRMT5 or WDR77 in MDA-MB-231 cells leads to defects in alternative splicing, including inclusion of A-T rich exons in target genes, a phenomenon that has previously been observed upon loss of ZNF326...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28966034/coordinated-splicing-of-regulatory-detained-introns-within-oncogenic-transcripts-creates-an-exploitable-vulnerability-in-malignant-glioma
#10
Christian J Braun, Monica Stanciu, Paul L Boutz, Jesse C Patterson, David Calligaris, Fumi Higuchi, Rachit Neupane, Silvia Fenoglio, Daniel P Cahill, Hiroaki Wakimoto, Nathalie Y R Agar, Michael B Yaffe, Phillip A Sharp, Michael T Hemann, Jacqueline A Lees
Glioblastoma (GBM) is a devastating malignancy with few therapeutic options. We identify PRMT5 in an in vivo GBM shRNA screen and show that PRMT5 knockdown or inhibition potently suppresses in vivo GBM tumors, including patient-derived xenografts. Pathway analysis implicates splicing in cellular PRMT5 dependency, and we identify a biomarker that predicts sensitivity to PRMT5 inhibition. We find that PRMT5 deficiency primarily disrupts the removal of detained introns (DIs). This impaired DI splicing affects proliferation genes, whose downregulation coincides with cell cycle defects, senescence and/or apoptosis...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28903384/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#11
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874563/epigenetic-control-via-allosteric-regulation-of-mammalian-protein-arginine-methyltransferases
#12
Kanishk Jain, Cyrus Y Jin, Steven G Clarke
Arginine methylation on histones is a central player in epigenetics and in gene activation and repression. Protein arginine methyltransferase (PRMT) activity has been implicated in stem cell pluripotency, cancer metastasis, and tumorigenesis. The expression of one of the nine mammalian PRMTs, PRMT5, affects the levels of symmetric dimethylarginine (SDMA) at Arg-3 on histone H4, leading to the repression of genes which are related to disease progression in lymphoma and leukemia. Another PRMT, PRMT7, also affects SDMA levels at the same site despite its unique monomethylating activity and the lack of any evidence for PRMT7-catalyzed histone H4 Arg-3 methylation...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28854561/sulforaphane-suppresses-prmt5-mep50-function-in-epidermal-squamous-cell-carcinoma-leading-to-reduced-tumor-formation
#13
Kamalika Saha, Matthew L Fisher, Gautam Adhikary, Daniel Grun, Richard L Eckert
Protein arginine methyltransferase 5 (PRMT5) cooperates with methylosome protein 50 (MEP50) to arginine methylate histone H3 and H4 to silence gene expression, and increased PRMT5 activity is associated with enhanced cancer cell survival. We have studied the role of PRMT5 and MEP50 in epidermal squamous cell carcinoma. We show that knockdown of PRMT5 or MEP50 results in reduced H4R3me2s formation, and reduced cell proliferation, invasion, migration and tumor formation. We further show that treatment with sulforaphane (SFN), a cancer preventive agent derived from cruciferous vegetables, reduces PRMT5 and MEP50 level and H4R3me2s formation, and this is associated with reduced cell proliferation, invasion and migration...
August 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#14
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#15
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28650658/potent-selective-and-cell-active-protein-arginine-methyltransferase-5-prmt5-inhibitor-developed-by-structure-based-virtual-screening-and-hit-optimization
#16
Ruifeng Mao, Jingwei Shao, Kongkai Zhu, Yuanyuan Zhang, Hong Ding, Chenhua Zhang, Zhe Shi, Hualiang Jiang, Dequn Sun, Wenhu Duan, Cheng Luo
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28591716/adapting-alphalisa-high-throughput-screen-to-discover-a-novel-small-molecule-inhibitor-targeting-protein-arginine-methyltransferase-5-in-pancreatic-and-colorectal-cancers
#17
Lakshmi Prabhu, Han Wei, Lan Chen, Özlem Demir, George Sandusky, Emily Sun, John Wang, Jessica Mo, Lifan Zeng, Melissa Fishel, Ahmad Safa, Rommie Amaro, Murray Korc, Zhong-Yin Zhang, Tao Lu
Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are notoriously challenging for treatment. Hyperactive nuclear factor κB (NF-κB) is a common culprit in both cancers. Previously, we discovered that protein arginine methyltransferase 5 (PRMT5) methylated and activated NF-κB. Here, we show that PRMT5 is highly expressed in PDAC and CRC. Overexpression of PRMT5 promoted cancer progression, while shRNA knockdown showed an opposite effect. Using an innovative AlphaLISA high throughput screen, we discovered a lead compound, PR5-LL-CM01, which exhibited robust tumor inhibition effects in both cancers...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28461757/novel-role-of-granulocyte-macrophage-colony-stimulating-factor-antitumor-effects-through-inhibition-of-epithelial-to-mesenchymal-transition-in-esophageal-cancer
#18
Jingxin Zhang, Qiqi Liu, Lili Qiao, Pingping Hu, Guodong Deng, Ning Liang, Jian Xie, Hui Luo, Jiandong Zhang
PURPOSE: Recent studies demonstrate the possible antitumor effects of granulocyte-macrophage colony-stimulating factor (GM-CSF); however, the exact mechanism is still unclear. The aim of our study was to analyze the effects of GM-CSF on multiple biological functions of human esophageal cancer (EC) cell lines and to explore the potential mechanism of its antitumor effects. MATERIALS AND METHODS: Eca109/9706 human EC cells were examined. Cell proliferation, apoptosis, and migration were analyzed using cell proliferation assay, flow cytometry, and transwell assay, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28397890/discovery-and-optimization-of-selective-inhibitors-of-protein-arginine-methyltransferase-5-by-docking-based-virtual-screening
#19
Yan Ye, Bidong Zhang, Ruifeng Mao, Chenhua Zhang, Yulan Wang, Jing Xing, Yu-Chih Liu, Xiaomin Luo, Hong Ding, Yaxi Yang, Bing Zhou, Hualiang Jiang, Kaixian Chen, Cheng Luo, Mingyue Zheng
Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme critical for diverse cellular processes and different types of cancers. Many efforts have been made to discover novel scaffold PRMT5 inhibitors. Herein, we report the discovery of DC_P33 as a hit compound of PRMT5 inhibitor, identified by molecular docking based virtual screening and (3)H-labeled radioactive methylation assays. Structure-activity relationship (SAR) analysis was performed on the analogs of DC_P33 and then structural modifications were done to improve its activity...
May 3, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28349379/ulva-pertusa-lectin-1-delivery-through-adenovirus-vector-affects-multiple-signaling-pathways-in-cancer-cells
#20
Gongchu Li, Zhenzhen Zhao, Bingbing Wu, Qunshu Su, Liqin Wu, Xinyan Yang, Jing Chen
Ulva pertusa lectin 1 (UPL1) is a N-acetyl-D-glucosamine (GlcNAc) binding lectin in marine green alga Ulva pertusa. Exogenous UPL1 colocalized with protein arginine methyltransferase 5 (PRMT5), methylosome protein 50 (MEP50), β-actin and β-tubulin, indicating the interaction of UPL1 with the methylosome and cytoskeleton. UPL1 delivery through adenovirus vector (Ad-UPL1) dramatically induced extracellularly regulated protein kinases 1/2 (ERK1/2) phosphorylation in liver cancer cell lines BEL-7404 and Huh7...
August 2017: Glycoconjugate Journal
keyword
keyword
58488
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"