Regulation of ADAM10 by miR-140-5p and potential relevance for Alzheimer's disease

Abstract

Recent reports in Alzheimer's disease (AD) research suggest that alterations in microRNA (miRNA) expression are associated with disease pathology. Our previous studies suggest that A Disintegrin and Metalloproteinase 10 (ADAM10) expression is important in AD and could be modulated by an extended regulatory region that includes the 3' untranslated region. In this study, we have investigated the role of trans-acting factors in ADAM10 gene regulation. Our study shows that miRNA-140-5p has enhanced expression in the AD postmortem brain hippocampus using high-throughput miRNA arrays and quantitative real-time polymerase chain reaction. Interestingly, we have also seen that miRNA-140-5p seed sequence is present on 3' untranslated region of both ADAM10 and its transcription factor SOX2. The specific interaction of miRNA-140-5p with both ADAM10 and SOX2 signifies high regulatory importance of this miRNA in controlling ADAM10 expression. Thus, this investigation unravels mechanisms underlying ADAM10 downregulation by miR-140-5p and suggests that dysfunctional regulation of ADAM10 expression is exacerbated by AD-related neurotoxic effects. These findings underscore the importance of understanding the impact of trans-acting factors in the modulation of AD pathophysiology.

Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress

“…MicroRNA (miRNA) is a single-stranded non-coding RNA, which can be used as potential drug targets to treat human diseases [12] , [13] , [14] , [15] . Previous studies showed that miR-140-5p has the biological activities including regulating adipocyte differentiation, inhibiting cancer growth and modulating Alzheimer's disease [16] , [17] , [18] . Furthermore, our previous work has also proved that miR-140-5p plays an important role in DOX- induced cardiotoxicity by inducing myocardial oxidative stress via targeting nuclear erythroid factor 2-related factor 2 (Nrf2) and silent information regulator factor 2-related enzyme 2 (Sirt2) [19] .…”

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

“…In addition to the ischemic stroke, many other diseases also exhibited dysregulated expression of miR-140-5p, such as hepatocellular carcinoma, colorectal cancer, and pulmonary arterial hypertension [28][29][30]. Previous reports also discovered various biological activities of miR-140-5p, including adipocyte differentiation regulation, cancer growth inhibition, as well as Alzheimer's disease modulation [31][32][33]. It is generally known that neuron protection is an important therapeutic target in ischemic stroke [34].…”

An investigation of microRNA‐103 and microRNA‐107 as potential blood‐based biomarkers for disease risk and progression of Alzheimer's disease

“…Furthermore, the contributions of miRNAs to AD development and progression have also been demonstrated to largely rely on their ability to alter the expression of toxic protein‐coding genes. For instance, miR‐140‐5p expression is enhanced in the AD postmortem brain hippocampus, and it downregulates ADAM10 that poses neuroprotective effect in early AD . The expression of miR‐29 is decreased in AD patients who have high levels of human β‐secretase, and employment of miR‐29 suppresses human β‐secretase‐induced Aβ peptide .…”