Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status

Kumar, Bhavna; Yadav, Arti; Brown, Nicole V.; Zhao, Songzhu; Cipolla, Michael J.; Wakely, Paul E.; Schmitt, Alessandra C.; Baiocchi, Robert A.; Teknos, Theodoros N.; Old, Matthew; Kumar, Pawan

doi:10.18632/oncotarget.14682

Cited by 26 publications

(24 citation statements)

References 50 publications

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“…in relation to cancer. PRMT5 acts as cancer-inducing gene by promoting cell proliferation (4)(5)(6)(7)(8), inhibiting transcription of tumor suppressor genes (4,(9)(10)(11)(12)(13) and inducing metastatic predisposition via epithelial-mesenchymal transition (14). The symmetric dimethylation of the arginine residues of histones H3 and H4 by PRMT5 triggers the modification of the chromatin structure and alterations in the expression patterns of diverse genes (3,(15)(16)(17).…”

Section: Protein Arginine Methyltransferase 5 Is Implicated In the Agmentioning

confidence: 99%

“…Additionally, PRMT5 induces transcriptional inhibition by directly methylating the tumor suppressor proteins p53 and E2F1, thus bestowing advantages for cancer cell survival (9,13). Recent studies have demonstrated that PRMT5 suppresses the expression of E-cadherin, the hallmark of EMT transition, through interactions with Ajuba and the E-cadherin transcription factor Snail (6,14). PRMT5 has been extensively characterized in relation to various types of cancer and its emerging role as a potential oncoprotein is of significant clinical interest.…”

Section: Protein Arginine Methyltransferase 5 Is Implicated In the Agmentioning

confidence: 99%

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Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells

et al. 2018

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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. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher α-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched non-tumor regions. Consistent with the significant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

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Section: Protein Arginine Methyltransferase 5 Is Implicated In the Agmentioning

confidence: 99%

Section: Protein Arginine Methyltransferase 5 Is Implicated In the Agmentioning

confidence: 99%

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells

et al. 2018

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“…For instance, high PRMT5 expression correlated with low overall survival and had over 1.7 times higher death risk than the patient who has low PRMT5 expression [41]. Together, these studies have identified PRMT5 as a promising therapeutic target in cancers.…”

Section: Histone Methylases As Potential Therapeutic Targets In Cancermentioning

confidence: 92%

Methylation of NF-κB and its Role in Gene Regulation

Wang¹,

Prabhu²,

Hartley³

et al. 2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

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The nuclear factor κB (NF-κB) is one of the most pivotal transcription factors in mammalian cells. In many pathologies NF-κB is activated abnormally. This contributes to the development of various disorders such as cancer, acute kidney injury, lung disease, chronic inflammatory diseases, cardiovascular disease, and diabetes. This book chapter focuses on how methylation of NF-κB regulates its target genes differentially. The knowledge from this chapter will provide scientific strategies for innovative therapeutic intervention of NF-κB in a wide range of diseases.

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“…PRMT5 deficiency also led to apoptosis in differentiated glioblastoma cells however, in glioblastoma neurospheres it led to G 1 cell cycle arrest through increased protein expression of p27 and a decrease in phosphorylation of pRb [ 120 ]. PRMT5 expression correlated with cyclin D1 protein levels, while also inversely correlating with p16 levels [ 121 ]. Nuclear PRMT5/p16-negative tumors were associated with poor prognosis in oropharyngeal squamous cell carcinoma when compared to nuclear PRMT5-negative/p16- positive tumors [ 121 ].…”

Section: Protein Arginine Methylationmentioning

confidence: 99%

“…PRMT5 expression correlated with cyclin D1 protein levels, while also inversely correlating with p16 levels [ 121 ]. Nuclear PRMT5/p16-negative tumors were associated with poor prognosis in oropharyngeal squamous cell carcinoma when compared to nuclear PRMT5-negative/p16- positive tumors [ 121 ]. PRMT5 is found to be overexpressed in many cancer types, including glioblastoma [ 118 , 122 ], lung [ 123 ], mantle cell lymphoma [ 124 ], ovarian [ 125 ] and prostate cancer [ 126 ].…”

Section: Protein Arginine Methylationmentioning

confidence: 99%

Protein arginine methylation: an emerging regulator of the cell cycle

Raposo¹,

Piller²

2018

Cell Div

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Protein arginine methylation is a common post-translational modification where a methyl group is added onto arginine residues of a protein to alter detection by its binding partners or regulate its activity. It is known to be involved in many biological processes, such as regulation of signal transduction, transcription, facilitation of protein–protein interactions, RNA splicing and transport. The enzymes responsible for arginine methylation, protein arginine methyltransferases (PRMTs), have been shown to methylate or associate with important regulatory proteins of the cell cycle and DNA damage repair pathways, such as cyclin D1, p53, p21 and the retinoblastoma protein. Overexpression of PRMTs resulting in aberrant methylation patterns in cancers often correlates with poor recovery prognosis. This indicates that protein arginine methylation is also an important regulator of the cell cycle, and consequently a target for cancer regulation. The effect of protein arginine methylation on the cell cycle and how this emerging key player of cell cycle regulation may be used in therapeutic strategies for cancer are the focus of this review.

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Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status

Cited by 26 publications

References 50 publications

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells

Methylation of NF-κB and its Role in Gene Regulation

Protein arginine methylation: an emerging regulator of the cell cycle

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