ArticleMolecular medicine (Cambridge, Mass.)2021
Weighted gene co-expression network-based approach to identify key genes associated with anthracycline-induced cardiotoxicity and construction of miRNA-transcription factor-gene regulatory network.
Article in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 22 citations in OpenAlex.
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- MicroRNA Signatures and Machine Learning Models for Predicting Cardiotoxicity in HER2-Positive Breast Cancer Patients.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation.Cancer medicine · 2025Article
- Mechanistic Insights into Flavonoid Subclasses as Cardioprotective Agents Against Doxorubicin-Induced Cardiotoxicity: A Comprehensive Review.Drug design, development and therapy · 2025Review
- MicroRNA composition of plasma extracellular vesicles: a harbinger of late cardiotoxicity of doxorubicin.Molecular medicine (Cambridge, Mass.) · 2022Article
- Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis.Oxidative medicine and cellular longevity · 2022Article
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7 authors at 2 institutions in 1 country.
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Abstract
backgroundCardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed.
methodsThe present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled.
resultsThe WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC.
conclusionsCollectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC.
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