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.

Machine learning-based identification of the novel circRNAs circERBB2 and circCHST12 as potential biomarkers of intracerebral hemorrhage

“…The combination of circERBB2 and circCHST12 with ICH risk factors increased the predictive value for the identification of ICH. These findings were better than the diagnostic value of three previously identified circRNAs [hsa_circ_0001240 (AUC = 0.808), hsa_circ_0001947 (AUC = 0.798) and hsa_circ_0001386 (AUC = 0.806)] in ICH (Bai et al, 2021). Additionally, we observed that downregulation of circERBB2 was positively associated with HDL-C and negatively correlated with SBP and DBP.…”

“…To elucidate the underlying mechanism by which the circRNAs affected ICH more specifically, we screened the common circRNAs in the two cohorts by both DESeq2 and edgeR methods (Supplementary Tables 1-4) and found that 9 circRNAs overlapped between the ICH patients and controls (Figure 3A). Similarly, there were 4 consistent circRNAs between ICH and hypertension (HTN) in our previous study (Figure 3B) (Bai et al, 2021); 2 of them were consistently altered in the two comparison groups, including hsa_circ_0027725 and a novel circRNA (host gene ERBB2) we named circERBB2 (Figure 3C).…”

“…RNA was isolated from human peripheral blood and used to perform RNA sequencing by Annoroad Gene Technology Company Ltd. (Beijing, China), as previously described ( Bai et al, 2021 ). Total RNA from all samples was isolated with an RNeasy Mini kit (QIAGEN).…”

“…Moreover, the expression of circRNAs was found to be significantly altered in IS ( Tiedt et al, 2017 ; Dong et al, 2020 ; Li et al, 2020 ; Lu et al, 2020 ; Ostolaza et al, 2020 ; Zuo et al, 2020 ), and these studies implied that aberrantly expressed circRNAs may be novel biomarkers for IS diagnosis and prognosis. Our previous study revealed that circRNA profiles were significantly altered in hypertensive ICH patients compared to hypertensive subjects without ICH and found that hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386 were potential biomarkers for predicting and diagnosing hypertensive ICH ( Bai et al, 2021 ). In addition, circRNA expression is significantly altered in rat brain tissue after ICH ( Dou et al, 2020 ; Zhong et al, 2020 ), indicating that circRNAs are novel clinical biomarkers for ICH.…”

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

“…Expression levels of three circRNAs (has_circ_0001240 and has_circ_0001947 were upregulated, and has_circ_0001386 was downregulated) were consistently altered (validated in an independent sample) in patients with ICH compared with their expression levels in patients with hypertension. Functional analysis in this study showed circRNAs to be mainly involved in fatty acid biogenesis, lysine degradation, integrin cell surface interactions and the immune system [ 81 ].…”