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MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.

ABSTRACT: Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significantly elevated in aneurysmal patients, although this did not correlate with the available clinical data. We then developed an in vitro model where, using cells with an endothelial phenotype, we determined the effect of miR-191 on the transcriptome using RNA sequencing. Subsequent pathway analysis established that some of the perturbations mediated by miR-191 can be explained by several processes which have long been observed and described in literature as accompanying the development of abdominal aortic aneurysms.

SUBMITTER: Licholai S

PROVIDER: S-EPMC8615628 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.

Lichołai Sabina S Studzińska Dorota D Plutecka Hanna H Gubała Tomasz T Szczeklik Wojciech W Sanak Marek M

Biomolecules 20211030 11

Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significa ...[more]

PMID: 34827608

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Project description:hsa-miR-191 is highly expressed in hepatocellular carcinoma (HCC), but the factors regulating this elevated expression are unknown. This study aimed to investigate the epigenetic mechanisms of increased hsa-miR-191 expression by analyzing the relationship between the DNA methylation status of hsa-miR-191 and miR-191 expression. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing PCR, Northern blot, and quantitative real-time PCR were performed to examine hsa-miR-191 methylation and expression levels. Western blot, transwell, and scratch assays were performed to examine the function and molecular mechanisms of hsa-miR-191. Approximately 58.9% of hsa-miR-191 expression was higher in HCC tissues than in adjacent noncancerous tissues; this high expression was associated with poor prognosis. The hypomethylation observed in some HCC cell lines and HCC tissues was correlated with the hsa-miR-191 expression level. This correlation was validated by treatment with the 5-aza-DAC demethylation agent. The level of hypomethylation was 63.0% in 73 clinical HCC tissue samples and was associated with increased (2.1-fold) hsa-miR-191 expression. The elevated expression of hsa-miR-191 in the SMMC-771 HCC cell line induced the cells to transition into mesenchymal-like cells; they exhibited characteristics such as loss of adhesion, down-regulation of epithelial cell markers, up-regulation of mesenchymal cell markers, and increased cell migration and invasion. Inhibiting hsa-miR-191 expression in the SMMC-7721 cell line reversed this process (as assessed by cell morphology and cell markers). Furthermore, hsa-miR-191 probably exerted its function by directly targeting TIMP metallopeptidase inhibitor 3 and inhibiting TIMP3 protein expression. Our results suggest that hsa-miR-191 locus hypomethylation causes an increase in hsa-miR-191 expression in HCC clinical tissues and that this expression induces HCC cells to transition into mesenchymal-like cells.

Dataset Information

MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.

Publications

MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.

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