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

Abstract

Objective

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 disease
• circular RNAs
• RNA sequencing
• radiation injuries
• microRNAs

Authors’ contributions

S.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 statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (81900356).

Notes on contributors

Shutong Shen

Shutong Shen, PhD, is a doctor at the Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China

Ping Lyu

Ping 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, China

Baixia Yang

Baixia Yang, PhD, is a doctor at the Department of Radiation Oncology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China

Xi Yang

Xi 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, China

Yida Li

Yida 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, China

Zhengfei Zhu

Zhengfei 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, China

Li Shen

Li Shen, PhD, is a professor at the Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China