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Updated: Sep 20, 2025
Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After Langendorff Perfusion
Published on: August 29, 2018
The whole transcriptome analysis and the circRNA-lncRNA network construction in arsenic trioxide-treated mice
Yanan Jiang1, Xiuyun Shen2, Chaorun Dong2
1Department of Pharmacology (State-Province Key Laboratories of Biomedicine, Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China; College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Background/Aims:
Arsenic trioxide (ATO) is an effective anti-cancer drug. Nonetheless, it possesses cardiotoxic effects which limit its clinical application. The present study aims to elucidate the molecular basis of ATO-induced cardiotoxicity through using whole transcriptome analysis.
Methods:
The whole transcriptome in ATO-treated mice myocardium was analyzed using RNA sequencing technique. These results were confirmed by real-time PCR. The lncRNA-mRNA and circRNA-mRNA co-expression networks were constructed. Finally, a circRNA-lncRNA co-regulated competing endogenous RNA (ceRNA) network was constructed. GO and KEGG pathway analyses were performed. The expression levels of Txnip and Spp1 in ATO-treated neonatal mouse cardiomyocytes were validated by real-time PCR.
Results:
A total of 113 mRNAs, 159 lncRNAs, 35 miRNAs, and 94 circRNAs were differentially expressed in ATO-treated mice myocardium. A lncRNA-circRNA co-regulation network was constructed. Function annotation revealed that aberrantly expressed genes may be enriched in the 'Wnt signaling pathway', 'Hippo signaling pathway', 'Notch signaling pathway', etc. Finally, the expression levels of Txnip and Spp1 were validated in ATO-treated cardiomyocytes, which was in accordance with the RNA-sequencing results.
Conclusion:
ATO altered coding and noncoding RNA profiles in myocardium of mice. The ATO-related lncRNA-circRNA co-regulation network was constructed. Genes in the co-regulation network are likely to play important roles in the cardiotoxicity of ATO. This study provides new insights into the prevention and treatment of ATO-induced cardiotoxicity.
Insights
Arsenic trioxide (ATO) causes cardiotoxicity by altering RNA profiles in the heart. This study reveals a novel lncRNA-circRNA network involved in ATO-induced cardiotoxicity, offering insights for treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Oncology
- Genomics
Background:
- Arsenic trioxide (ATO) is a potent anti-cancer agent but its clinical use is limited by cardiotoxicity.
- Understanding the molecular mechanisms underlying ATO-induced cardiotoxicity is crucial for safe application.
Purpose of the Study:
- To elucidate the molecular basis of arsenic trioxide-induced cardiotoxicity.
- To identify key coding and non-coding RNAs involved in this process using whole transcriptome analysis.
Main Methods:
- Whole transcriptome analysis (RNA sequencing) of arsenic trioxide-treated mouse myocardium.
- Construction of lncRNA-mRNA, circRNA-mRNA, and circRNA-lncRNA co-expression networks.
- Gene Ontology (GO) and KEGG pathway analyses, followed by real-time PCR validation of specific gene expressions.
Main Results:
- Differential expression of 113 mRNAs, 159 lncRNAs, 35 miRNAs, and 94 circRNAs in arsenic trioxide-treated myocardium.
- Construction of a lncRNA-circRNA co-regulation network.
- Identification of enriched signaling pathways including Wnt, Hippo, and Notch, with validated expression of Txnip and Spp1.
Conclusions:
- Arsenic trioxide significantly alters coding and non-coding RNA profiles in the heart.
- A novel arsenic trioxide-related lncRNA-circRNA co-regulation network was identified.
- This network provides new molecular targets and insights for preventing and treating arsenic trioxide-induced cardiotoxicity.
