Comprehensive analysis of differentially expressed serum microRNAs in humans responding to Brucella infection

Abstract

Background: MicroRNAs (miRNAs), a subset of small non-coding RNA molecules, play crucial roles in various pathophysiological processes. Studies increasingly indicate that dysregulated miRNAs are associated with bacterial infection. Nevertheless, little is known about miRNAs that respond to Brucella infection and their potential clinical value. Our research aimed to identify the serum miRNAs altered during Brucella infection. Methods: We enrolled serum samples from 73 patients diagnosed with brucellosis and 65 age-and sexmatched control individuals. Illumina sequencing via synthesis (SBS) technology was performed for an initial screen of miRNAs expression profile in serum samples pooled from 29 patients and 29 controls, respectively. A quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted in the training and validation sets to confirm the concentrations of differentially expressed miRNAs in individual serum samples from 73 patients and 65 controls.Results: The Illumina SBS technology identified 1,372 known miRNAs and 1,893 novel miRNAs in brucellosis patients. The three markedly upregulated miRNAs (miR-15a-3p, miR-7-2-3p, miR-103b) in brucellosis patients were subsequently validated by qRT-PCR assay, of which miR-103b was confirmed to be significantly and steadily increased in the brucellosis patients compared with the controls (>2-fold, P<0.001).The area under the receiver operating characteristic (ROC) curve (AUC) for miR-103b was 0.714 (95% CI, 0.624-0.804). Bioinformatics analysis predicted that some putative target genes of miR-103b are involved in immune regulation or the processes of apoptosis and autophagy in humans. Conclusions:The serum miR-103b level markedly increases after Brucella infection and has the potential to serve as an auxiliary diagnostic indicator for Brucella infection that deserves further investigation.

microRNAs in human brucellosis: A promising therapeutic approach and biomarker for diagnosis and treatment

“…Currently, several miRNAs such as miR-125b-5p, miR-369-5p, miR-586, miR-520f-3p, miR-4307, miR-505-3p, miR-4516, miR-2861, miR-3960, miR-126-5p, miR-4753-5p, miR-181b, miR-1981, miR-7-2-3p, miR-15a-3p, miR-103b, mmu-miR-199a-3p, mmu-miR-183-5p, miR-130a-3p, miR-181a, miR-301a-3p, miR-146a, and miR-351-5p have been found that have a role in the immunopathogenesis of brucellosis. 16,[21][22][23][24][25][26][27][28][29] In the following, we overview these miRNAs in brucellosis.…”

“…16 Specifically, a whole of 25 target genes participates in the regulation of autophagy and apoptosis, suggesting that specific miRNAs can perform a crucial regulative function in Brucella-host interaction. 16 Zhang et al 29 identified 1372 miRNAs using Illumina sequencing via synthesis technology and 1893 new miRNAs identified in brucellosis. The miR-15a-3p, miR-7-2-3p, and miR-103b were upregulated in cases with brucellosis, that miR-103b a significant increase in brucellosis patients compared to the healthy group.…”

“…[15][16][17][18][19][20] Currently, it has been found that several miRNAs (including miR-125b-5p, miR-21-5p, miR-23b, miR-155, miR-301a-3p, mmu-miR-183-5p, miR-130a-3p, miR-146a, mmu-miR-199a-3p, miR-181a-5P, and miR-351-5p and among others) have a role in the immunopathogenesis of Brucellosis. 16,[21][22][23][24][25][26][27][28][29] For example, miR-125 is a suppressor or promoter in various disorders and could induce the nuclear factor-κB (NF-κB) via targeting A20. In a study, Liu et al 26 noticed decreasing the levels of miR-125b-5p during B. abortus infection increased the A20 expression.…”

Brucellosis in China: history, progress and challenge

“…Although there are many studies on Brucella infection, few studies have been devoted to exploring the effects of brucellosis on serum miRNA expression, however miR-103b has been highlighted. Further exploration and validation are required to evaluate the potential target genes of miR-103b and their relationship with the occurrence and development of brucellosis [17].…”

Exploration of microRNA profiles in human colostrum

“…They are important regulators of many biological processes, such as organogenesis, body development, cellular metabolism, and cell differentiation (3). Moreover, miRNAs have unique stable expression patterns in various body fluids, including saliva (4), serum (5,6), plasma (7), and urine (8). Therefore, miRNAs can be used as non-invasive or minimally invasive biomarkers for a range of diseases, as well as potential indicators for the quality of food products (9).…”