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

English version

Autoři: Neire Niara Ferreira de Araujo ^aff001; Hui Tzu Lin-Wang ^aff002; Juliana de Freitas Germano ^aff003; Pedro Silvio Farsky ^aff001; Andre Feldman ^aff001; Fabio Henrique Rossi ^aff004; Nilo Mitsuru Izukawa ^aff004; Maria de Lourdes Higuchi ^aff005; Felicio Savioli Neto ^aff001; Mario Hiroyuki Hirata ^aff002; Marcelo Chiara Bertolami ^aff001
Působiště autorů: Department of Clinical Cardiology, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil ^aff001; Laboratory of Molecular Investigation in Cardiology, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil ^aff002; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil ^aff003; Department of Vascular Surgery, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil ^aff004; Laboratory of Cardiac Pathology, Heart Institute, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil ^aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222782

Souhrn

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.

Klíčová slova:

Biology and life sciences – Genetics – Gene expression – Biochemistry – Nucleic acids – Research and analysis methods – Proteins – Molecular biology – Neuroscience – Gene regulation – Molecular biology techniques – Medicine and health sciences – Pathology and laboratory medicine – RNA – Non-coding RNA – Artificial gene amplification and extension – Polymerase chain reaction – Neurochemistry – Neurochemicals – Vascular medicine – Natural antisense transcripts – MicroRNAs – Vascular diseases – Aneurysms – Pathogenesis – Eicosanoids – Elastin

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