Identification of Circular RNA Expression Profiles and Potential Biomarkers for Intracerebral Hemorrhage

Abstract

Aim: To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). Materials & methods: RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Results: Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. The circRNAs were involved mainly in lysine degradation and the immune system. Conclusion: This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.

Lay abstract

The expression profiles of circular RNAs (circRNAs) and their potential roles in intracerebral hemorrhage (ICH; also known as stroke) are still unclear. We demonstrated for the first time that circRNA expression levels were different in patients with ICH. The expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in patients with hypertension (high blood pressure). We confirmed that hsa_circ_0001240 and hsa_circ_0001947 were upregulated and hsa_circ_0001386 was downregulated in ICH compared with their levels in hypertensive patients. These three circRNAs, individually or combined, are novel promising biomarkers for predicting and diagnosing ICH. The target mRNAs of the three circRNAs are involved mainly in specific amino acid degradation and the immune system. This is the first study to report expression profiles of circRNAs after ICH and to propose three circRNAs as potential biomarkers for ICH.

Graphical abstract

Work flow.

CI: Cerebral infarction; FC: Fold change; FDR: False discovery rate; HTN: Hypertension; ICH: Intracerebral hemorrhage.

Keywords::

• biomarkers
• circular RNA
• functional analysis
• intracerebral hemorrhage
• RNA sequencing

C Bai wrote the manuscript. H Li, J Ping, H Xu and J Chen revised the manuscript. C Bai, M Zhang and Y Feng analyzed the data. C Bai and L Song performed the experiment of circRNA expression levels. T Liu, J Ge and X Wang enrolled the samples and investigated the clinical data. H Li and N Xiao checked the programs of statistical analysis. Y Sun recorded the samples and data analysis. J Chen conceived and designed the study and supervised all the sample selection, data analysis and interpretation. All authors read and approved the final manuscript.

Financial & competing interests disclosure

The study was supported by the National Basic Research Program of China (2014CB541601 to J Chen), the CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2016-I2M-1-015 to J Chen). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The data that support the findings in this study are available from corresponding author on reasonable request.

Additional information

Funding

The study was supported by the National Basic Research Program of China (2014CB541601 to J Chen), the CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2016-I2M-1-015 to J Chen). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.