Open AccessDysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues
Author(s) -
Neire Niara Ferreira de Araújo,
Hui Tzu Lin-Wang,
Juliana de Freitas Germano,
Pedro Sílvio Farsky,
André Feldman,
Fábio Henrique Rossi,
Nilo Mitsuru Izukawa,
Maria de Lourdes Higuchi,
Francisco Barbosa de Araújo Neto,
Mário Hiroyuki Hirata,
Marcelo Chiara Bertolami
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0222782
Subject(s) - microrna , abdominal aortic aneurysm , biomarker , biology , gene , pathogenesis , bioinformatics , medicine , aneurysm , genetics , immunology , surgery
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.