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MicroRNA-29a-3p regulates abdominal aortic aneurysm development and progression via direct interaction with PTEN
Yuan Zhou1, Meigui Wang1, Jing Zhang2
1Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Abstract:
Various research studies have been conducted in deducing the role of microRNAs (miRNAs) in the pathogenesis and physiological processes of various systematic diseases. This study aims at demonstration of the important role played by miR-29a-3p, through association with phosphatase and tensin homolog (PTEN), in the regulation of abdominal aortic aneurysm development and progression. Quantitative real-time polymerase chain reaction (RT-qPCR) examined miRNA-19a-3p and PMEPA1 expression in multiplied vascular smooth muscle cells (VSMCs). Cell transfection upregulated or downregulated the genes and cell counting kit-8 assay determined cellular viability. RT-qPCR detected cellular proliferation and cell death using the cell proliferation and apoptosis biomarkers Ki87 and proliferating cell nuclear antigen, caspase-8 and caspase-3, respectively. Furthermore, luciferase assay analyzed the luciferase activity and western blot analysis determined miRNA-19a-3p and PMEPA1 protein expression in proliferation and apoptosis biomarkers. TargetScan 4.2 online software (www.targetscan.org) was used to perform the bioinformatics analysis so as to forecast the putative targets of miR-29a-3p and PTEN. The results inferred that there was an increased expression of miRNA-29a-3p found in AAA-mimic cells with increased cellular viability and significant pathological apoptosis. Further, when the expression of miRNA-29a-3p was downregulated, it reduced the cell viability of AAA cells. On the basis of the gene interplays, it can be understood that the PTEN was directly targeted by miRNA-29a-3p so as to regulate the AAA progression. Thus, PTEN was found to strengthen the proliferation effect of miRNA-29a-3p in AAA cells. The current study thus shed more insights about the molecular mechanistic roles of miRNA-29a-3p and PTEN, opening doors for novel therapeutic approach to AAA.
Insights
MicroRNA-29a-3p plays a key role in abdominal aortic aneurysm (AAA) development by targeting PTEN. Downregulating miR-29a-3p reduces AAA cell viability, offering potential therapeutic strategies.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial in regulating physiological processes and disease pathogenesis.
- Abdominal aortic aneurysm (AAA) is a life-threatening condition with complex molecular mechanisms.
- Understanding miRNA involvement in AAA is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the role of miR-29a-3p in the development and progression of abdominal aortic aneurysm (AAA).
- To elucidate the association between miR-29a-3p and phosphatase and tensin homolog (PTEN) in AAA pathogenesis.
- To explore potential therapeutic targets for AAA based on miRNA-PTEN interactions.
Main Methods:
- Quantitative real-time polymerase chain reaction (RT-qPCR) to assess gene expression.
- Cell transfection to modulate gene expression, followed by cell viability assays (Cell Counting Kit-8).
- Analysis of proliferation and apoptosis markers, luciferase assays, western blotting, and bioinformatics (TargetScan 4.2).
Main Results:
- Increased miR-29a-3p expression was observed in AAA-mimic cells, correlating with higher cell viability and apoptosis.
- Downregulation of miR-29a-3p significantly reduced the viability of AAA cells.
- Bioinformatics and experimental data confirmed that PTEN is a direct target of miR-29a-3p, with PTEN enhancing miR-29a-3p's proliferative effect in AAA.
Conclusions:
- miR-29a-3p directly targets PTEN, playing a significant role in regulating AAA development and progression.
- The miR-29a-3p/PTEN axis represents a novel molecular mechanism in AAA pathogenesis.
- This study provides insights for developing new therapeutic strategies targeting the miR-29a-3p/PTEN pathway for AAA treatment.
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