1. Department of health inspection and quarantine, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China;
2. Shenzhen Key Lab of Health Science and Technology, Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
3. Institute of Disease Control and Prevention, Shenzhen International Travel Health Care Center, Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518048, China;
4. School of Life Sciences, Biochemistry Programme, The Chinese University of Hong Kong, Room 609, Mong Man Wai Building, Shatin, NT, Hong Kong, China;
5. Clinical Laboratory, Third People's Hospital, Nanhai District, Foshan City, Guangdong 528244, China.
Objectives: Pathological biomarkers and mechanisms of dengue infection are poorly understood. We investigated a new serum biomarker using miRNAs and performed further correlation analysis in dengue-infected patients.
Methods: Expression levels of broad-spectrum miRNAs in serum samples from three patients with dengue virus type 1 (DENV-1) and three healthy volunteers were separately analyzed using miRNA PCR arrays. The expressions of the five selected miRNAs were verified by qRT-PCR in the sera of 40 DENV-1 patients and compared with those from 32 healthy controls. Receiver operating characteristic (ROC) curve and correlation analyses were performed to evaluate the potential of these miRNAs for the diagnosis of dengue infection.
Results: MiRNA PCR arrays revealed that 41 miRNAs were upregulated, whereas 12 miRNAs were down-regulated in the sera of DENV-1 patients compared with those in healthy controls. Among these miRNAs, qRT-PCR validation showed that serum hsa-miR-21-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were upregulated, whereas hsa-miR-146a-5p was down-regulated in dengue-infected patients compared with healthy controls. ROC curves showed serum hsa-miR-21-5p and hsa-miR-146a-5p could distinguish dengue-infected patients with preferable sensitivity and specificity. Correlation analysis indicated that expression levels of serum hsa-miR-21-5p and hsa-miR-146a-5p were negative and positively correlated with the number of white blood cells and neutrophils, respectively. Functional analysis of target proteins of these miRNAs in silico indicated their involvement in inflammation and cell proliferation.
Conclusion: Dengue-infected patients have a broad “fingerprint” profile with dysregulated serum miRNAs. Among these miRNAs, serum hsa-miR-21-5p, hsa-miR-146a-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were identified as promising serum indicators for dengue infection.
Keywords: microRNA, dengue, miRNA-21-5p, miRNA-146a-5p, miR-590-5p, miR-188-5p, miR-152-3p.