Evidence map›Paper›PMID 39181539›Full record

ArticleJournal of thrombosis and haemostasis : JTH2024

RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.

Liying Guan, Deepak Voora, Rachel Myers, Fabiola Del Carpio-Cano, A Koneti Rao

Abstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Transcription factor RUNX1 regulates coagulation factor XIII-A (Research and practice in thrombosis and haemostasis · 2025
    Article
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Liying GuanSol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
Deepak VooraDepartment of Medicine, Duke University, Durham, North Carolina, USA.
Rachel MyersDuke Clinical Research Unit, Duke University School of Medicine, Durham, North Carolina, USA.
Fabiola Del Carpio-CanoSol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
A Koneti RaoSol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA; Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA. Electronic address: koneti@temple.edu.

Funding

Human Platelet Defects in Transcription Factor RUNX1 HaplodeficiencyR01HL109568 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RAO, ANGARA KONETI · 2013 to 2022
$3.4M
Runx1 Haplodeficiency, Endocytosis and Vesicle transportR01HL137376 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RAO, ANGARA KONETI · 2018 to 2021
$1.8M
NHLBI NIH HHS R01 HL109568NHLBI NIH HHS R01 HL137376
6 · The paper itself

Abstract

backgroundHematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoters to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream gene regulation in megakaryocytes and platelets are unknown.

objectivesTo understand the regulation of RUNX1 and its target genes by RUNX1 isoforms.

methodsWe performed studies on RUNX1 isoforms in megakaryocytic human erythroleukemia (HEL) cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD).

resultsIn chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells, RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5A, and others) differentially in HEL cells. In platelets, RUNX1B transcripts (by RNA sequencing) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively with F13A1, PCTP, PDE5A, RAB1B, and others, and negatively with MYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targets F13A1 and RAB31 associated with acute events.

conclusionRUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner, and this is associated with acute events in CVD.

Indexed as

Blood PlateletsCore Binding Factor Alpha 2 SubunitGene Expression RegulationMegakaryocytesPromoter Regions, GeneticProtein IsoformsAgedCardiovascular DiseasesFemaleHeLa CellsHumansMaleMiddle AgedTicagrelorCore Binding Factor Alpha 2 SubunitProtein IsoformsRUNX1 protein, humanTicagrelorautoregulationcardiovascular diseasemegakaryocytesplateletsRUNX1

Identifiers

PMID39181539
PMCPMC11608153

What Socratic holds

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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 Socratic graph.