Evidence map›Paper›PMID 35263585›Full record

ArticleCell reports2022

Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.

Gabriela Krivdova, Veronique Voisin, Erwin M Schoof, Sajid A Marhon, Alex Murison, Jessica L McLeod, Martino M Gabra, Andy G X Zeng, Stefan Aigner, Brian A Yee and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
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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

25 authors.

Gabriela KrivdovaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A5, Canada.
Veronique VoisinThe Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
Erwin M SchoofPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Sajid A MarhonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Alex MurisonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Jessica L McLeodPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Martino M GabraDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Andy G X ZengPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A5, Canada.
Stefan AignerDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Brian A YeeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Alexander A ShishkinDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Eric L Van NostrandDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Karin G HermansPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Program of Developmental & Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G0A4, Canada.
Aaron C Trotman-GrantPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Nathan MbongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
James A KennedyPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Division of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, Toronto, ON M4N3M5, Canada.
Olga I GanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Elvin WagenblastPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Daniel D De CarvalhoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Leonardo SalmenaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Gary D BaderPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A5, Canada; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A5, Canada. Electronic address: john.dick@uhnresearch.ca.
Eric R LechmanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address: eric.lechman@uhnresearch.ca.

Funding

Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
A Comprehensive Functional Map of Human Protein-RNA InteractionsU41HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R. · 2018 to 2021
$9.4M
A comprehensive binding and functional map of human RNA-binding proteinsU24HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R., YEO, EUGENE WEI-MING · 2022 to 2025
$5.5M
Robust, high-throughput identification of RNA processing regulators and regulatory networks genome-wideR00HG009530 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI VAN NOSTRAND, ERIC LYMAN · 2020 to 2022
$747k
Robust, high-throughput identification of RNA processing regulators and regulatory networks genome-wideK99HG009530 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VAN NOSTRAND, ERIC LYMAN · 2017 to 2018
$250k
NHGRI NIH HHS K99 HG009530NHGRI NIH HHS R00 HG009530NHGRI NIH HHS R01 HG004659NHGRI NIH HHS U24 HG009889NHGRI NIH HHS U41 HG009889
6 · The paper itself

Abstract

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed in t(8;21) acute myeloid leukemia (AML), where it is critical for maintaining the oncogenic molecular program mediated by the AML1-ETO complex. Our study establishes that identification of the comprehensive miRNA targetome within primary cells enables discovery of genes and molecular networks underpinning stemness properties of normal and leukemic cells.

Indexed as

Leukemia, Myeloid, AcuteMicroRNAsCell Line, TumorCell Self RenewalHematopoietic Stem CellsHumansReceptors, Cytoplasmic and NuclearRepressor ProteinsMicroRNAsReceptors, Cytoplasmic and NuclearRepressor ProteinsTBL1XR1 protein, human21) AMLacute myeloid leukemiaAML1-ETOchimeric AGO2 eCLIP-seqhematopoietic stem cellmicroRNAmolecular networkself-renewalstemnesst(8TBL1XR1

Identifiers

PMID35263585
PMCPMC11185845

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.