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Prmt5 cancer

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https://www.readbyqxmd.com/read/29749478/protein-arginine-methyltransferase-5-is-implicated-in-the-aggressiveness-of-human-hepatocellular-carcinoma-and-controls-the-invasive-activity-of-cancer-cells
#1
Ju-Yeon Jeon, Jee San Lee, Eun-Ran Park, Yan Nan Shen, Mi-Yeun Kim, Hyun-Jin Shin, Hyun-Yoo Joo, Eung-Ho Cho, Sun Mi Moon, Ui Sup Shin, Sun Hoo Park, Chul Ju Han, Dong Wook Choi, Man Bock Gu, Sang-Bum Kim, Kee-Ho Lee
Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2...
April 25, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29724292/arginine-methyltransferase-inhibitor-1-exhibits-antitumor-effects-against-cervical-cancer-in-vitro-and-in-vivo
#2
Shu-Hong Dong, Xing Wang, San-Chun Tian, Neng-Qian Ma, Xin-Yang Zhang, Yapeng Liu, Bao-Lai Zhang, Yong-Jie Wu
Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in several types of tumors including cervical cancer. Arginine methyltransferase inhibitor 1 (AMI-1) inhibits solid tumors by targeting PRMT5. However, the effect of AMI-1 on cervical cancer is still unknown. In this study, we provided the first evidence that AMI-1 reduced cervical cancer cell proliferation, colony formation and promoted cell apoptosis in vitro. Suppression of tumorigenicity was also confirmed in vivo. Mechanistic studies revealed that AMI-1 significantly reduced PRMT5 level in cells and mice xenografts model of cervical cancer...
May 1, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29721098/capg-enhances-breast-cancer-metastasis-by-competing-with-prmt5-to-modulate-stc-1-transcription
#3
Sheng Huang, Yayun Chi, Yi Qin, Ziliang Wang, Bingqiu Xiu, Yonghui Su, Rong Guo, Liang Guo, Hefen Sun, Chujia Zeng, Shuling Zhou, Xin Hu, Sheng Liu, Zhimin Shao, Zhaohui Wu, Wei Jin, Jiong Wu
Macrophage-capping protein (CAPG) has been shown to promote cancer cell metastasis, although the mechanism remains poorly understood. Methods: Breast cancer (BC) tissue microarray was used to test the role of CAPG in the prognosis of BC patients. Xenograft mice model was used to validate the metastasis promotion role of CAPG in vivo. Gene expression array, chromatin immunoprecipitation and luciferase report assay were performed to search for the target genes of CAPG. Protein immunoprecipitation, MS/MS analysis, tissue microarray and histone methyltransferase assay were used to explore the mechanism of CAPG regulating stanniocalcin 1 (STC-1) transcription...
2018: Theranostics
https://www.readbyqxmd.com/read/29683372/modulating-the-expression-of-chtop-a-versatile-regulator-of-gene-specific-transcription-and-mrna-export
#4
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29679612/protein-arginine-methyltransferase-5-promotes-lung-cancer-metastasis-via-the-epigenetic-regulation-of-mir-99-family-fgfr3-signaling
#5
Pengyu Jing, Nan Zhao, Mingxiang Ye, Yong Zhang, Zhipei Zhang, Jianyong Sun, Zhengxin Wang, Jian Zhang, Zhongping Gu
Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome...
April 18, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29603824/expression-of-protein-arginine-methyltransferase-5-in-oral-squamous-cell-carcinoma-and-its-significance-in-epithelial-to-mesenchymal-transition
#6
Yusuke Amano, Daisuke Matsubara, Taichiro Yoshimoto, Tomoko Tamura, Hiroshi Nishino, Yoshiyuki Mori, Toshiro Niki
Protein arginine methyltransferases (PRMT) 5, a member of type II arginine methyltransferases, catalyzes the symmetrical dimethylation of arginine residues on histone and non-histone substrates. Although the overexpression of PRMT5 has been reported in various cancers, its role in oral squamous cell carcinoma (OSCC) has not been elucidated. In the present study, we immunohistochemically examined the expression of PRMT5 in surgically resected oral epithelial dysplasia (OED, n = 8), oral intraepithelial neoplasia (OIN)/carcinoma in situ (CIS) (n = 11) and OSCC (n = 52) with or without contiguous OED lesions...
March 30, 2018: Pathology International
https://www.readbyqxmd.com/read/29545752/identification-of-a-novel-protein-arginine-methyltransferase-5-inhibitor-in-non-small-cell-lung-cancer-by-structure-based-virtual-screening
#7
Qianqian Wang, Jiahui Xu, Ying Li, Jumin Huang, Zebo Jiang, Yuwei Wang, Liang Liu, Elaine Lai Han Leung, Xiaojun Yao
Protein arginine methyltransferase 5 (PRMT5) is able to regulate gene transcription by catalyzing the symmetrical dimethylation of arginine residue of histone, which plays a key role in tumorigenesis. Many efforts have been taken in discovering small-molecular inhibitors against PRMT5, but very few were reported and most of them were SAM-competitive. EPZ015666 is a recently reported PRMT5 inhibitor with a new binding site, which is different from S-adenosylmethionine (SAM)-binding pocket. This new binding site provides a new clue for the design and discovery of potent and specific PRMT5 inhibitors...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29529599/lncrna-snhg16-functions-as-an-oncogene-by-sponging-mir-4518-and-up-regulating-prmt5-expression-in-glioma
#8
Ye-Fen Lu, Xue-Li Cai, Zheng-Zheng Li, Jing Lv, Yi-An Xiang, Jian-Jun Chen, Wei-Jing Chen, Wei-Yan Sun, Xiu-Mei Liu, Jian-Bo Chen
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. METHODS: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed...
March 6, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29501774/protein-arginine-methyltransferase-5-mediates-enolase-1-cell-surface-trafficking-in-human-lung-adenocarcinoma-cells
#9
Dariusz Zakrzewicz, Miroslava Didiasova, Marcus Krüger, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas C Hocke, Anna Zakrzewicz, Liliana Schaefer, Klaus T Preissner, Malgorzata Wygrecka
OBJECTIVES: Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface. RESULTS: We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29449933/a-simplified-characterization-of-s-adenosyl-l-methionine-consuming-enzymes-with-1-step-ez-mtase-a-universal-and-straightforward-coupled-assay-for-in-vitro-and-in-vivo-setting
#10
Emmanuel S Burgos, Ryan O Walters, Derek M Huffman, David Shechter
Methyltransferases use S -adenosyl-l-methionine (SAM) to deposit methyl marks. Many of these epigenetic 'writers' are associated with gene regulation. As cancer etiology is highly correlated with misregulated methylation patterns, methyltransferases are emerging therapeutic targets. Successful assignment of methyltransferases' roles within intricate biological networks relies on (1) the access to enzyme mechanistic insights and (2) the efficient screening of chemical probes against these targets. To characterize methyltransferases in vitro and in vivo , we report a highly-sensitive one-step deaminase-linked continuous assay where the S -adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and quantitatively catabolized to S -inosyl-l-homocysteine (SIH)...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29441724/prmt5-promotes-cell-proliferation-by-inhibiting-btg2-expression-via-the-erk-signaling-pathway-in-hepatocellular-carcinoma
#11
Hai Jiang, Yue Zhu, Zhenyu Zhou, Junyang Xu, Shaowen Jin, Kang Xu, Heyun Zhang, Qing Sun, Jie Wang, Junyao Xu
Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, has roles in cell growth regulation and cancer development. However, the role of PRMT5 in hepatocellular carcinoma (HCC) progression remains unclear. Here, we showed that PRMT5 expression was frequently upregulated in HCC tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. We revealed that the mechanism of PRMT5-induced proliferation was partially mediated by BTG downregulation, leading to cell cycle arrest during the G1 phase in HCC cells...
March 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29262329/prmt5-is-a-critical-regulator-of-breast-cancer-stem-cell-function-via-histone-methylation-and-foxp1-expression
#12
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
#13
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
#14
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...
January 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29185119/prmt5-determines-the-sensitivity-to-chemotherapeutics-by-governing-stemness-in-breast-cancer
#15
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...
April 2018: 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
#16
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
#17
REVIEW
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...
November 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29017049/exploiting-the-hidden-treasure-of-detained-introns
#18
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
#19
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)...
December 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28977470/the-prmt5-wdr77-complex-regulates-alternative-splicing-through-znf326-in-breast-cancer
#20
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...
November 2, 2017: Nucleic Acids Research
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