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Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus.

ABSTRACT: Circular RNAs (circRNAs) have emerged as novel biomarkers for disease diagnosis. However, the expression profiles and clinical significance of circRNAs in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) remain unclear. In the present study, the expression profile of circRNAs in PBMCs from patients with SLE and healthy controls (HCs) was detected by using microarray analysis and verified by reverse transcription?quantitative polymerase chain reaction. A total of 1,603 circRNAs were identified to be significantly aberrantly expressed in PBMCs from patients with SLE. Validation assays in 30 SLE patients and 20 HCs demonstrated that the levels of hsa_circ_0044235 and hsa_circ_0068367 were significantly decreased in the patients with SLE. Receiver operating characteristic curve analysis suggested that hsa_circ_0044235 and hsa_circ_0068367 were significant for SLE diagnosis. Furthermore, the diagnostic potential of hsa_circ_0044235 and hsa_circ_0068367 for SLE was validated in an independent validation set with 45 patients with SLE, 38 HCs and 30 patients with rheumatoid arthritis. In addition, the level of hsa_circ_0044235 in the PBMCs from patients with SLE were identified to be significantly increased in new?onset SLE patients and in patients who were determined to be positive for anti?double?stranded DNA and anti?ribosomal protein P antibodies. Additionally, the level of a microRNA (miRNA) target of hsa_circ_0044235, hsa?miRNA?892a, was identified to be significantly increased in the PBMCs from patients with SLE. The present study suggested that the dysregulation of circRNAs may serve a role in SLE pathogenesis, and that the levels of hsa_circ_0044235 and hsa_circ_0068367 in PBMC have potential as biomarkers for SLE diagnosis.

SUBMITTER: Luo Q

PROVIDER: S-EPMC6713423 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus.

Luo Qing Q Zhang Lu L Li Xue X Fu Biqi B Guo Yang Y Huang Zikun Z Li Junming J

International journal of molecular medicine 20190805 4

Circular RNAs (circRNAs) have emerged as novel biomarkers for disease diagnosis. However, the expression profiles and clinical significance of circRNAs in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) remain unclear. In the present study, the expression profile of circRNAs in PBMCs from patients with SLE and healthy controls (HCs) was detected by using microarray analysis and verified by reverse transcription‑quantitative polymerase chain reaction. A total of ...[more]

PMID: 31432107

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Project description:BackgroundSystemic Lupus Erythematosus (SLE), a prototypical autoimmune disorder, presents a challenge due to the absence of reliable biomarkers for discerning organ-specific damage within SLE. A growing body of evidence underscores the pivotal involvement of N6-methyladenosine (m6A) in the etiology of autoimmune conditions.MethodsThe datasets, which primarily encompassed the expression profiles of m6A regulatory genes, were retrieved from the Gene Expression Omnibus (GEO) repository. The optimal model, selected from either Random Forest (RF) or Support Vector Machine (SVM), was employed for the development of a predictive nomogram model. To identify pivotal genes associated with SLE, a comprehensive screening process was conducted utilizing LASSO, SVM-RFE, and RF techniques. Within the realm of SLE susceptibility, Weighted Gene Co-expression Network Analysis (WGCNA) was harnessed to delineate relevant modules and hub genes. Additionally, MeRIP-qPCR assays were performed to elucidate key genes correlated with m6A targets. Furthermore, a Mendelian randomization study was conducted based on genome-wide association studies to assess the causative influence of MMP9 on ischemic stroke (IS), which is not only a severe cerebrovascular event but also a common complication of SLE.ResultsTwelve m6A regulatory genes was identified, demonstrating statistical significance (p < 0.05) and utilized for constructing a nomogram model using the RF algorithm. EPSTI1, USP18, HP, and MMP9, as the hub genes, were identified. MMP9 uniquely correlates with m6A modification and was causally linked to an increased risk of IS, as indicated by our inverse variance weighting analysis showing an odds ratio of 1.0134 (95% CI=1.0004-1.0266, p = 0.0440).ConclusionOur study identified twelve m6A regulators, shedding light on the molecular mechanisms underlying SLE risk genes. Importantly, our analysis established a causal relationship between MMP9, a key m6A-related gene, and ischemic stroke, a common complication of SLE, thereby providing critical insights for presymptomatic diagnostic approaches.

Dataset Information

Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus.

Publications

Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus.

Similar Datasets

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