Evidence map›Paper›PMID 31822509›Full record

ArticleThe Journal of biological chemistry2020

Protein arginine methyltransferase 5 represses tumor suppressor miRNAs that down-regulate CYCLIN D1 and c-MYC expression in aggressive B-cell lymphoma.

Vrajesh Karkhanis, Lapo Alinari, Hatice Gulcin Ozer, Jihyun Chung, Xiaoli Zhang, Saïd Sif, Robert A Baiocchi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  5. Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024
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  14. Presence of theFrontiers in oncology · 2022
    Article
  15. Overexpression of PTPRZ1 Regulates p120/Journal of oncology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Vrajesh KarkhanisDivision of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
Lapo AlinariDivision of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
Hatice Gulcin OzerDepartment of Biomedical Informatics, Ohio State University, Columbus, Ohio 43210.
Jihyun ChungDivision of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
Xiaoli ZhangCenter for Biostatistics, Department of Biomedical Informatics, Ohio State University, Columbus, Ohio 43210.
Saïd SifDepartment of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, P. O. Box 2713, Doha, Qatar ssif@qu.edu.qa.ORCID 0000-0001-6268-1145
Robert A BaiocchiDivision of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210 robert.baiocchi@osumc.edu.
The Ohio State University · USQatar University · QA

Funding

Project 3: Targeting PRMT5 in Mantle Cell LymphomaP01CA214274 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI BAIOCCHI, ROBERT ALAN · 2018 to 2022
$8.9M
NCI NIH HHS P01 CA214274
6 · The paper itself

Abstract

Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma, and supports constitutive expression of CYCLIN D1 and c-MYC. Here, we combined ChIP analysis with next-generation sequencing to identify microRNA (miRNA) genes that are targeted by PRMT5 in aggressive lymphoma cell lines. We identified enrichment of histone 3 dimethylation at Arg-8 (H3(Me2)R8) in the promoter regions of miR33b, miR96, and miR503. PRMT5 knockdown de-repressed transcription of all three miRNAs, accompanied by loss of recruitment of epigenetic repressor complexes containing PRMT5 and either histone deacetylase 2 (HDAC2) or HDAC3, enhanced binding of co-activator complexes containing p300 or CREB-binding protein (CBP), and increased acetylation of specific histones, including H2BK12, H3K9, H3K14, and H4K8 at the miRNA promoters. Re-expression of individual miRNAs in B-cell lymphoma cells down-regulated expression of PRMT5, CYCLIN D1, and c-MYC, which are all predicted targets of these miRNAs, and reduced lymphoma cell survival. Luciferase reporter assays with WT and mutant 3'UTRs of CYCLIN D1 and c-MYC mRNAs revealed that binding sites for miR33b, miR96, and miR503 are critical for translational regulation of the transcripts of these two genes. Our findings link altered PRMT5 expression to transcriptional silencing of tumor-suppressing miRNAs in lymphoma cells and reinforce PRMT5's relevance for promoting lymphoma cell growth and survival.

Indexed as

3' Untranslated RegionsAcetylationChromatin Immunoprecipitation SequencingCREB-Binding ProteinCyclin D1Down-RegulationE1A-Associated p300 ProteinGene SilencingGenes, Tumor SuppressorHistone DeacetylasesHistonesHumansLymphoma, B-CellMethylationMicroRNAsPromoter Regions, Genetic3' Untranslated RegionsCREB-Binding ProteinCyclin D1E1A-Associated p300 ProteinEP300 protein, humanHistone DeacetylasesHistonesMicroRNAsMIRN33b microRNA, humanMIRN503 microRNA, humanMIRN96 microRNA, humanMYC protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesProto-Oncogene Proteins c-myccancercyclin D1epigeneticsgene regulationhistone deacetylase (HDAC)lymphomamicroRNA (miRNA)Myc (c-Myc)post-translational modificationPRMT5

Identifiers

PMID31822509
PMCPMC6996892
OpenAlexW2995889831

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.