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. 2019 Sep 20;14(9):e0222782.
doi: 10.1371/journal.pone.0222782. eCollection 2019.

Dysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues

Neire Niara Ferreira de Araujo  1 , Hui Tzu Lin-Wang  2 , Juliana de Freitas Germano  3 , Pedro Silvio Farsky  1 , Andre Feldman  1 , Fabio Henrique Rossi  4 , Nilo Mitsuru Izukawa  4 , Maria de Lourdes Higuchi  5 , Felicio Savioli Neto  1 , Mario Hiroyuki Hirata  2   3 , Marcelo Chiara Bertolami  1
Affiliations

Dysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues

Neire Niara Ferreira de Araujo et al. PLoS One. .

Abstract

Background: Abdominal aortic aneurysm (AAA) is a pathological enlargement of infrarenal aorta close to the aortic bifurcation, and it is an important cause of mortality in the elderly. Therefore, the biomarker identification for early diagnosis is of great interest for clinical benefit. It is known that microRNAs (miRNAs) have important roles via target genes regulation in many diseases. This study aimed to identify miRNAs and their target genes involved in the pathogenesis of AAA.

Methods: Tissue samples were obtained from patients who underwent AAA surgery and from organ donors (control group). Quantitative PCR Array was applied to assess 84 genes and 384 miRNAs aiming to identify differentially expressed targets (AAA n = 6, control n = 6), followed by validation in a new cohort (AAA n = 18, control n = 6) by regular qPCR. The functional interaction between validated miRNAs and target genes was performed by the Ingenuity Pathway Analysis (IPA) software.

Results: The screening cohort assessed by PCR array identified 10 genes and 59 miRNAs differentially expressed (≥2-fold change, p<0.05). Among these, IPA identified 5 genes and 9 miRNAs with paired interaction. ALOX5, PTGIS, CX3CL1 genes, and miR-193a-3p, 125b-5p, 150-5p maintained a statistical significance in the validation cohort. IPA analysis based on the validated genes and miRNAs revealed that eicosanoid and metalloproteinase/TIMP synthesis are potentially involved in AAA.

Conclusion: Paired interactions of differentially expressed ALOX5, PTGIS, CX3CL1 genes, and miR-193b-3p, 125b-5p, 150-5p revealed a potentially significant role of the eicosanoid synthesis and metalloproteinase/TIMP pathways in the AAA pathogenesis.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Validation of gene expression by qPCR.
The relative expression was calculated using the 2-ΔΔCt formula and Mann-Whitney test was performed to compare AAA (n = 18) and control groups (n = 6). The null hypothesis was rejected if the p-value was lower than 0.05.
Fig 2
Fig 2. Validation of microRNA expression by qPCR.
The 2-ΔΔCt formula was applied to obtain relative expression and Mann-Whitney test was performed to compare AAA (n = 18) and control group (n = 6). The null hypothesis was rejected if the p-value waslower than 0.05.
Fig 3
Fig 3. Ingenuity Pathway Analysis (IPA) showed predicted interactions between validated miRNAs and their respective targets genes in abdominal aortic aneurysm.
Intermediary molecules are also showed in grey to clarify the connections of miRNAs and targets. The blue lines and molecules represent inhibition; orange lines and molecules represent activation; green represents miRNA down-regulation, and red represents miRNA up-regulation.
See this image and copyright information in PMC

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