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Identification and Functional Analysis of Circular RNAs in Ankylosing Spondylitis Patient Peripheral Blood Mononuclear Cells
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  • Dan Huang,
  • Jian Liu,
  • YUAN WANG,
  • Lei Wan,
  • Yanyan Fang,
  • Xiang Ding,
  • Wandong Zhang
Dan Huang
The First Affiliated Hospital of Anhui University of Chinese Medicine Department of Pharmacy
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Jian Liu
Anhui College of Traditional Chinese Medicine

Corresponding Author:[email protected]

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YUAN WANG
Anhui University of Traditional Chinese Medicine
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Lei Wan
Anhui University of Traditional Chinese Medicine
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Yanyan Fang
Anhui University of Traditional Chinese Medicine
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Xiang Ding
Anhui University of Traditional Chinese Medicine
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Wandong Zhang
The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine
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Abstract

Objectives:To analyze the function and roles of circRNAs in the peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients. Methods: The expression of AS-related circRNAs were detected by high-throughput RNA-sequencing within the PBMCs of 5 AS cases and healthy controls. After profiling circRNA expression in these samples, differentially expressed circRNAs (DECs) were identified, and a qPCR-based validation approach was used to confirm the differential expression of six of these DECs in patient samples. Spearman’s correlation tests and ROC curve analyses were further used to assess the relationship between disease severity and the expression of DECs of interest in AS patients, after which a putative circRNA-microRNAs (miRNAs) interaction network was constructed leading to the detection of six validated DECs with competing endogenous RNA (ceRNA) functionality. Besides, cell experiments were also performed to investigate the potential mechanism of key circRNA in AS. Results: 10,441 circRNAs were identified in these 10 PBMC samples, with 131 total DECs including 89 and 42 that were up- and down-regulated, respectively. In qPCR validation assays, patterns of hsa_circ_0000702, hsa_circ_0006209, hsa_circ_0047920, hsa_circ_0001543, hsa_circ_0072697 and hsa_circ_0005076 were confirmed to align well with RNA-seq results. In addition, the expression levels of hsa_circ_0006209, hsa_circ_0047920, and hsa_circ_0072697 were detected to be positively correlated with disease severity. ROC curve analyses suggested that hsa_circ_0072697 may offer value as a diagnostic biomarker for AS. Cell experiments indicated that hsa_circ_0072697 could suppress the progression of AS by targeting NF-κB pathway Conclusions: The identification of six circRNAs with putative ceRNA functionality in AS patients highlights potential molecular mechanisms governing this debilitating disease. However, further research will be necessary to formally confirm the roles of these DECs and their target miRNAs in AS. Further, hsa_circ_0072697 has a good diagnostic value in AS patients, and it could suppress the progression of AS by targeting NF-κB pathwa