MicroRNA‐29a‐3p regulates abdominal aortic aneurysm development and progression via direct interaction with PTEN

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 (http://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.

Sox6 expression and aneurysms of the thoracic and abdominal aorta

“…The immune-related gene JCHAIN (joining chain of multimeric IgA and IgM) and the guanine nucleotide exchange factor DENND1C (DENN domain containing 1C) had the highest fold increase in AAA (Figure 3B). IPA showed that several canonical pathways previously associated with AAA development [27][28][29][30] are upregulated in AAA samples, including Th2 and Th1 pathways, PTEN signaling, and oxidative stress in macrophages (Figure 3C). Most of the upregulated functions identified by IPA are related to immune responses known to play a role in AAA [27][28][29][30] (Figure 3D and Supplementary Figure 4).…”

miR‐29a‐3p promotes migration and invasion in ameloblastoma via Wnt/β‐catenin signaling by targeting catenin beta interacting protein 1

“…It was reported that miR-29a-3p can inhibit tumor progression by targeting different genes in studies of colorectal carcinoma, 11 acute myeloid leukemia, 12 gastric cancer, 13,14 and hepatocellular carcinoma. 15 However, other studies showed that miR-29a-3p promotes cell proliferation, migration, and invasion in tumors, such as abdominal aortic aneurysms, 16 gastric cancer with Helicobacter pylori infection, 17 gliomas, 18 and hepatocellular carcinomas with hepatitis B virus infection. 19 miR-29a-3p was found to target COL1A1 to improve the radiotherapy sensitivity of nasopharyngeal carcinoma cells.…”

Beneficial role of microRNA‑328‑3p in fracture healing by enhancing osteoblastic viability through the PTEN/PI3K/AKT pathway

“…According to bioinformatics prediction, PTEN was identified as a target gene of miR-328-3p, and its interaction with miR-328-3p was demonstrated using a luciferase reporter assay. PTEN is a key molecule involved in various cellular processes (30,31). For example, PTEN acted as a target gene of miR-29a-3p and could mediate the regulatory effects of miR-29a-39 on vascular smooth muscle cell proliferation and apoptosis (30).…”

“…PTEN is a key molecule involved in various cellular processes (30,31). For example, PTEN acted as a target gene of miR-29a-3p and could mediate the regulatory effects of miR-29a-39 on vascular smooth muscle cell proliferation and apoptosis (30). Another example demonstrated that the regulatory role of methyltransferase-like protein 3 (METTL3) regulated retinal pigment epithelium cell proliferation, apoptosis and pyroptosis by inhibiting PTEN (31).…”