Noncoding RNA-associated competing endogenous RNA networks in trastuzumab-induced cardiotoxicity

Suifen Xie; Ni Zhou; Nan Su; Zijun Xiao; Shanshan Wei; Yuanying Yang; Jian Liu; Wenqun Li; Bikui Zhang

doi:10.1016/j.ncrna.2024.02.004

Noncoding RNA-associated competing endogenous RNA networks in trastuzumab-induced cardiotoxicity

Noncoding RNA Res. 2024 Feb 22;9(3):744-758. doi: 10.1016/j.ncrna.2024.02.004. eCollection 2024 Sep.

Authors

Suifen Xie^{1

2

3}, Ni Zhou^{1

2

3}, Nan Su⁴, Zijun Xiao^{1

2}, Shanshan Wei^{1

2}, Yuanying Yang^{1

2}, Jian Liu^{1

2}, Wenqun Li^{1

2}, Bikui Zhang^{1

2}

Affiliations

¹ Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
² Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, 410011, China.
³ Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, China.
⁴ Department of Ophthalmology, The First People's Hospital of Lanzhou City, Lanzhou, 730050, Gansu Province, China.

Abstract

Trastuzumab-induced cardiotoxicity (TIC) is a common and serious disease with abnormal cardiac function. Accumulating evidence has indicated certain non-coding RNAs (ncRNAs), functioning as competing endogenous RNAs (ceRNAs), impacting the progression of cardiovascular diseases. Nonetheless, the specific involvement of ncRNA-mediated ceRNA regulatory mechanisms in TIC remains elusive. The present research aims to comprehensively investigate changes in the expressions of all ncRNA using whole-transcriptome RNA sequencing. The sequencing analysis unveiled significant dysregulation, identifying a total of 43 circular RNAs (circRNAs), 270 long noncoding RNAs (lncRNAs), 12 microRNAs (miRNAs), and 4131 mRNAs in trastuzumab-treated mouse hearts. Subsequently, circRNA-based ceRNA networks consisting of 82 nodes and 91 edges, as well as lncRNA-based ceRNA networks comprising 111 nodes and 112 edges, were constructed. Using the CytoNCA plugin, pivotal genes-miR-31-5p and miR-644-5p-were identified within these networks, exhibiting potential relevance in TIC treatment. Additionally, KEGG and GO analyses were conducted to explore the functional pathways associated with the genes within the ceRNA networks. The outcomes of the predicted ceRNAs and bioinformatics analyses elucidated the plausible involvement of ncRNAs in TIC pathogenesis. This insight contributes to a better understanding of underlying mechanisms and aids in identifying promising targets for effective prevention and treatment strategies.

Keywords: Cardiotoxicity; Noncoding RNA; Trastuzumab; Whole transcriptome sequencing; ceRNA networks.