Identification of circRNAs and circRNA-miRNA-mRNA regulatory network in radiation-induced heart disease

AbstractObjective Radiation-induced heart disease (RIHD) is one of the most common and serious long-term adverse effect after thoracic radiotherapy. Our aim was to investigate the potential molecular mechanism underlying RIHD using RNA-sequencing (RNA-seq) and bioinformatics methods.Materials and methods An RIHD rat model was established and transcription profiles were identified using RNA-seq. Differentially expressed circRNAs, miRNAs and mRNAs were identified. Enrichment of functions and signaling pathways analysis were performed based on GO and the KEGG database. Potential circRNA-miRNA-mRNA regulatory network underlying RIHD was established. qRT-PCR was used to validate the associated genes.Results In total, 21 circRNAs, 26 miRNAs, and 178 mRNA transcripts were differentially expressed in RIHD. GO and KEGG pathway analyses identified that differentially expressed mRNAs were most enriched in pathways referring to endothelial function and vascular pathological processes. Nine circRNAs, 10 miRNAs, and 6 mRNA transcripts were most likely involved in vascular function and a candidate competitive endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA was established, which were further validated by qRT-PCR.Conclusions Our study revealed that vascular pathology plays an important role in the early stage of RIHD. Furthermore, a circRNA-miRNA-mRNA ceRNA network was found that may be involved in the regulation of vascular function and RIHD.Keywords: Radiation-induced heart diseasecircular RNAsRNA sequencingradiation injuriesmicroRNAs Authors' contributionsS.T.S., P.L., and B.X.Y. performed the experiments. S.T.S., X.Y., and Y.D.L performed the bioinformatics analyses. S.T.S. drafted the manuscript. L.S. designed the study and Z.F.Z. participated in its design and helped to draft the manuscript. All authors read and approved the final manuscript.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by grants from the National Natural Science Foundation of China (81900356).Notes on contributorsShutong ShenShutong Shen, PhD, is a doctor at the Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, ChinaPing LyuPing Lyu, PhD, is a doctor at the Department of Cardiology, The First People's Hospital of Nantong, The Second Affiliated Hospital of Nantong University, Nantong, ChinaBaixia YangBaixia Yang, PhD, is a doctor at the Department of Radiation Oncology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, ChinaXi YangXi Yang, PhD, is a doctor at the Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaYida LiYida Li, PhD, is a researcher at the Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaZhengfei ZhuZhengfei Zhu, PhD, is a professor at the Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaLi ShenLi Shen, PhD, is a professor at the Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China