Evidence map›Paper›PMID 40158615›Full record

ArticleLife sciences2025

SiRNA-mediated knockdown of TOP2B protects hiPSC-derived cardiomyocytes from doxorubicin-induced toxicity.

Neha Saroj, Pankaj Singh Dholaniya, Syed Baseeruddin Alvi, Divya Sridharan, Navisha Soni, Syed Abdullah Ashraf, Ayza Choudhry, Yusuf Ali Ashraf, Sarah Kathleen Mikula, Dinender Kumar Singla and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025
    Review
  4. Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025
    Review
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

11 authors.

Neha SarojDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Pankaj Singh DholaniyaDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India. Electronic address: pankajsingh.dholaniya@osumc.edu.
Syed Baseeruddin AlviDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Divya SridharanDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Navisha SoniDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Syed Abdullah AshrafDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Ayza ChoudhryDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Yusuf Ali AshrafDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Sarah Kathleen MikulaCenter for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA.
Dinender Kumar SinglaBiomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
Mahmood KhanDivision of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH, USA; Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA. Electronic address: Mahmood.Khan@osumc.edu.

Funding

Amelioration of Doxorubicin Induced Muscle Dysfunction with Embryonic Stem Cell-Derived ExosomesR01CA221813 · NCI · UNIVERSITY OF CENTRAL FLORIDA · PI KUKREJA, RAKESH C, SINGLA, DINENDER KUMAR · 2018 to 2024
$3.1M
Molecular identity of exosomal BK channelsR01HL157453 · NHLBI · OHIO STATE UNIVERSITY · PI Mahmood Khan, HARPREET SINGH · 2022 to 2026
$3.0M
Biomimetic cardiac patch capable of rapid angiogenesisR01HL136232 · NHLBI · OHIO STATE UNIVERSITY · PI KHAN, MAHMOOD · 2017 to 2021
$2.8M
In Situ Skin Regeneration and Angiogenesis for Full-Thickness BurnsR01AR080946 · NIAMS · OHIO STATE UNIVERSITY · PI Mahmood Khan, Heather M Powell · 2023 to 2026
$2.3M
NCI NIH HHS R01 CA221813NHLBI NIH HHS R01 HL136232NHLBI NIH HHS R01 HL157453NIAMS NIH HHS R01 AR080946
6 · The paper itself

Abstract

aimsDoxorubicin (Dox) is a potent chemotherapeutic agent, but its use is limited by cardiotoxicity, primarily due to the disruption of Topoisomerase-2 beta (TOP2B) activity. Dexrazoxane (Dex), an FDA-approved cardioprotective drug, alleviates Dox-induced toxicity but lacks heart-specific targeting. This study investigates siRNA-mediated TOP2B knockdown as a more targeted strategy to protect cardiomyocytes from Dox-induced damage. MATERIALS AND

methodsHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with siRNA to knock down TOP2B and were then exposed to Dox. We compared the cardioprotective effects of siRNA-mediated knockdown to Dex treatment using cell viability, cell toxicity assay and electrophysiological evaluation was performed using a multielectrode array (MEA). KEY

findingsOur results demonstrate that TOP2B silencing significantly decreases apoptosis and improved cell viability, as compared to the Dex treatment. Additionally, electrophysiological assays using a Multielectrode Array (MEA) demonstrated enhanced contractility and conductivity in siRNA-treated hiPSC-CMs. Furthermore, transmission electron microscopy (TEM) data revealed that TOP2B knockdown preserves mitochondrial morphology and sarcomere structure, compared to Dox and Dex-treated groups. SIGNIFICANCE: These findings suggest that siRNA-mediated TOP2B inhibition could provide a safer, more specific approach to mitigate Dox-induced cardiotoxicity.

Indexed as

Antibiotics, AntineoplasticCardiotoxicityDNA Topoisomerases, Type IIDoxorubicinInduced Pluripotent Stem CellsMyocytes, CardiacPoly-ADP-Ribose Binding ProteinsRNA, Small InterferingApoptosisCell SurvivalDexrazoxaneGene Knockdown TechniquesHumansAntibiotics, AntineoplasticDexrazoxaneDNA Topoisomerases, Type IIDoxorubicinPoly-ADP-Ribose Binding ProteinsRNA, Small InterferingTOP2B protein, humanApoptosisCardioprotectionCardiotoxicityDexrazoxaneDoxorubicinhiPSC-CMssiRNA knockdownTOP2B

Identifiers

PMID40158615
PMCPMC13312502

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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.