Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

Abstract

MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA.

MiR‐195 promotes abdominal aortic aneurysm media remodeling by targeting Smad3

“…22 MiR-103a has been revealed to exert inhibitory effect on AAA growth by targeting ADAM10. 23 Our present study focuses on the role of miR-195 in AAA progression and found that miR-195 was up-regulated in the aortic media of AAA patients, which was consistent with the finding reported by Zampetaki et al 10 However, the potential mechanisms of miR-195 involved in AAA pathology is far from being addressed.…”

“…Ectopic expression of miR‐145 by lentivirus infection apparently reduced the incidence of AAA . MiR‐103a has been revealed to exert inhibitory effect on AAA growth by targeting ADAM10 . Our present study focuses on the role of miR‐195 in AAA progression and found that miR‐195 was up‐regulated in the aortic media of AAA patients, which was consistent with the finding reported by Zampetaki et al .…”

Exosomal miR‐103a‐3p ameliorates lipopolysaccharide‐induced immune response in BEAS‐2B cells via NF‐κB pathway by targeting transducin β‐like 1X related protein 1

“…MiRNAs are non‐coding RNAs, and can mediate cell proliferation, apoptosis and other biological functions by targeting multiple transcription factors . Previous studies have confirmed that ADAM10 was a target of miR‐103a‐3p, and silencing of ADAM10 abated the inflammation of murine abdominal aorta . Moreover, miR‐103a‐3p negatively regulates PTEN expression, leads to the increased expression of immunosuppressive factors in lung cancer cells .…”

Stage‐dependent involvement of ADAM10 and its significance in epileptic seizures

“…A previous study showed increased promoter activity for an ADAM10 promoter‐luciferase construct compared to an ADAM10 promoter‐luciferase‐3′‐UTR construct in SH‐SY5Y cells, indicating the involvement of miRNAs in the posttranscriptional regulation of ADAM10 . Several miRNAs targeting ADAM10 have been reported in pathological conditions, such as tumours and AD . However, the miRNAs involved in these pathological conditions nearly overlap; hence, the involvement of miRNAs in ADAM10 regulation is most likely disease specific, necessitating the development of disease‐specific strategies for treating ADAM10‐related diseases (Figure ; Table ).…”

“…57 Several miRNAs targeting ADAM10 have been reported in pathological conditions, such as tumours and AD. [66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] However, the miRNAs involved in these pathological conditions nearly overlap; hence, the involvement of miRNAs in ADAM10 regulation is most likely disease specific, necessitating the development of disease-specific strategies for treating ADAM10-related diseases ( Figure 1; Table 1). miRNA/ADAM10 pathways have been primarily defined in tumours and AD but are undetermined in epilepsy.…”