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

被引:13
作者
Ferreira de Araujo, Neire Niara [1 ]
Lin-Wang, Hui Tzu [2 ]
Germano, Juliana de Freitas [3 ]
Farsky, Pedro Silvio [1 ]
Feldman, Andre [1 ]
Rossi, Fabio Henrique [4 ]
Izukawa, Nilo Mitsuru [4 ]
Higuchi, Maria de Lourdes [5 ]
Savioli Neto, Felicio [1 ]
Hirata, Mario Hiroyuki [2 ,3 ]
Bertolami, Marcelo Chiara [1 ]
机构
[1] Dante Pazzanese Inst Cardiol, Dept Clin Cardiol, Sao Paulo, Brazil
[2] Dante Pazzanese Inst Cardiol, Lab Mol Invest Cardiol, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, Brazil
[4] Dante Pazzanese Inst Cardiol, Dept Vasc Surg, Sao Paulo, Brazil
[5] Univ Sao Paulo, Sch Med, Heart Inst, Lab Cardiac Pathol, Sao Paulo, Brazil
来源
PLOS ONE | 2019年 / 14卷 / 09期
关键词
5-LIPOXYGENASE PATHWAY; SMOOTH-MUSCLE; LET-7; PATHOGENESIS; ASSOCIATION; EXPRESSION; BIOMARKERS; CHEMOKINE; MODELS;
D O I
10.1371/journal.pone.0222782
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 miR193b-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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页数:14
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