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

Abstract

BackgroundAbdominal 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.MethodsTissue 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.ResultsThe 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.ConclusionPaired 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.

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

“…Similar to what occurred in plasma, the results in tissue samples differ among studies. As previously reported [ 10 , 15 , 23 , 44 , 45 ], we have observed a downregulation of miR-133b, miR-29b-3p, and miR-27b-3p in AAA tissue, whereas other authors found them upregulated [ 9 , 46 ]. In the case of miR-21-5p, most studies report an increase in AAA tissue [ 9 , 15 , 22 ], while only one group found a decrease [ 21 ].…”

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

“… hsa-miR-503 Targets Rictor (mTOR complex 2 signaling element), promotes tumor progression [ 69 ], promotes ESCC cell proliferation, migration, and invasion by targeting cyclin D1 [ 73 ], negative regulator of proliferation in primary human cells [ 74 ]. hsa-miR-542 Upregulated in AAA patients [ 42 ]. hsa-miR-548d Associated with schizophrenia [ 75 ].…”

Identification of Circ-FNDC3B, an Overexpressed circRNA in Abdominal Aortic Aneurysm, as a Regulator of Vascular Smooth Muscle Cells

“…By combining target prediction and expression modulation analysis, we first demonstrated that circ-FNDC3B directly targeted miR-143-3p, a down-regulated miRNA in AAA tissues. 15) MiR-143-3p has been established as an antitumor factor in multiple cancers, such as pancreatic ductal adenocarcinoma, osteosarcoma, and nasal squamous cell carcinoma. [23][24][25] Previous works also uncovered that several other circRNAs, such as circ_0003998 and circRNA casein kinase 1 gamma 3, acted as potent miR-143-3p sponges in human carcinogenesis.…”

“…13,14) MiR-143-3p was underexpressed in abdominal aortic tissues of patients with AAA using miRNA qPCR array analysis. 15) However, the biological function of miR-143-3p in AAA development remains to be elucidated. Moreover, it is still unclear whether the action of circ-FNDC3B in the development of AAA is mediated by miR-143-3p.…”