Evidence map›Paper›PMID 31077320›Full record

ArticleJournal of the National Cancer Institute2020

Uncovering the Role of RNA-Binding Protein hnRNP K in B-Cell Lymphomas.

Miguel Gallardo, Prerna Malaney, Marisa J L Aitken, Xiaorui Zhang, Todd M Link, Vrutant Shah, Sanzhar Alybayev, Meng-Han Wu, Laura R Pageon, Huaxian Ma and 12 more

Open access · greenAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021
    Pooled it
  2. Article
  3. Review
  4. NMolecular medicine (Cambridge, Mass.) · 2024
    Review
  5. Article
  6. The Role of RNA-Binding Proteins in Hematological Malignancies.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. RNA-binding motifs of hnRNP K are critical for induction of antibody diversification by activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 2 countries.

Miguel GallardoDepartment of Leukemia.
Prerna MalaneyDepartment of Leukemia.
Marisa J L AitkenDepartment of Leukemia.
Xiaorui ZhangDepartment of Leukemia.
Todd M LinkDepartment of Genomic Medicine.
Vrutant ShahDepartment of Epigenetics and Molecular Carcinogenesis.
Sanzhar AlybayevDepartment of Molecular Oncology.
Meng-Han WuDepartment of Leukemia.
Laura R PageonDepartment of Veterinary Medicine and Surgery.
Huaxian MaDepartment of Leukemia.
Rodrigo JacamoDepartment of Leukemia.
Li YuDepartment of Hematopathology.
Zijun Y Xu-MonetteDepartment of Hematopathology.
Haley SteinmanDepartment of Leukemia.
Hun Ju LeeDepartment of Lymphoma and Myeloma The University of Texas, MD Anderson Cancer Center, Houston, TX.
Dos SarbassovDepartment of Molecular Oncology.
Inmaculada RapadoDepartment of Hematology, Hospital Universitario Madrid, Spain.
Michelle C BartonDepartment of Epigenetics and Molecular Carcinogenesis.
Joaquin Martinez-LopezDepartment of Hematology, Hospital Universitario Madrid, Spain.
Carlos Bueso-RamosDepartment of Hematopathology.
Ken H YoungDepartment of Hematopathology.
Sean M PostDepartment of Leukemia.
Hospital Universitario HM Madrid · ESThe University of Texas MD Anderson Cancer Center · USSpanish National Cancer Research Centre · ES

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Convergence of MicroRNAs and p53 Signaling in Multiple Myeloma: Environmental CoR01CA138688 · NCI · UNIVERSITY OF LOUISVILLE · PI LI, YONG · 2009 to 2017
$2.9M
Personalized therapy for AML patients with a newly identified genetic alterationR01CA207204 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI POST, SEAN M · 2016 to 2020
$1.8M
Deep Sequencing of Small Regulatory RNAs in Diffuse Large B cell LymphomaRC1CA146299 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI XIAO, CHANGCHUN · 2009 to 2010
$1000k
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA138688NCI NIH HHS R01 CA207204NCI NIH HHS RC1 CA146299
6 · The paper itself

Abstract

backgroundHeterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA-binding protein that is aberrantly expressed in cancers. We and others have previously shown that reduced hnRNP K expression downmodulates tumor-suppressive programs. However, overexpression of hnRNP K is the more commonly observed clinical phenomenon, yet its functional consequences and clinical significance remain unknown.

methodsClinical implications of hnRNP K overexpression were examined through immunohistochemistry on samples from patients with diffuse large B-cell lymphoma who did not harbor MYC alterations (n = 75). A novel transgenic mouse model that overexpresses hnRNP K specifically in B cells was generated to directly examine the role of hnRNP K overexpression in mice (three transgenic lines). Molecular consequences of hnRNP K overexpression were determined through proteomics, formaldehyde-RNA-immunoprecipitation sequencing, and biochemical assays. Therapeutic response to BET-bromodomain inhibition in the context of hnRNP K overexpression was evaluated in vitro and in vivo (n = 3 per group). All statistical tests were two-sided.

resultshnRNP K is overexpressed in diffuse large B-cell lymphoma patients without MYC genomic alterations. This overexpression is associated with dismal overall survival and progression-free survival (P < .001). Overexpression of hnRNP K in transgenic mice resulted in the development of lymphomas and reduced survival (P < .001 for all transgenic lines; Line 171[n = 30]: hazard ratio [HR] = 64.23, 95% confidence interval [CI] = 26.1 to 158.0; Line 173 [n = 31]: HR = 25.27, 95% CI = 10.3 to 62.1; Line 177 [n = 25]: HR = 119.5, 95% CI = 42.7 to 334.2, compared with wild-type mice). Clinical samples, mouse models, global screening assays, and biochemical studies revealed that hnRNP K's oncogenic potential stems from its ability to posttranscriptionally and translationally regulate MYC. Consequently, Hnrnpk overexpression renders cells sensitive to BET-bromodomain-inhibition in both in vitro and transplantation models, which represents a strategy for mitigating hnRNP K-mediated c-Myc activation in patients.

conclusionOur findings indicate that hnRNP K is a bona fide oncogene when overexpressed and represents a novel mechanism for c-Myc activation in the absence of MYC lesions.

Indexed as

Disease SusceptibilityAdultAgedAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalFemaleGene ExpressionGene Expression Regulation, NeoplasticHeterogeneous-Nuclear Ribonucleoprotein KHumansLymphoma, B-CellMaleMiceMice, TransgenicAntineoplastic AgentsHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanRNA-Binding Proteins

Identifiers

PMID31077320
PMCPMC7489062
OpenAlexW2944131629

What OpenQuestion holds

Textmetadata
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Registered trials

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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.