Dysregulation of MicroRNAs and Target Genes Networks in Human Abdominal Aortic Aneurysm Tissues

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Sep 21

PMID 31539405

Citations 7

Authors

Neire Niara Ferreira de Araujo

Hui Tzu Lin-Wang

Juliana de Freitas Germano

Pedro Silvio Farsky

Andre Feldman

Fabio Henrique Rossi

Nilo Mitsuru Izukawa

Maria de Lourdes Higuchi

Felicio Savioli Neto

Mario Hiroyuki Hirata

Marcelo Chiara Bertolami

Affiliations

Soon will be listed here.

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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