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3 publications mentioning mml-mir-181a-1

Open access articles that are associated with the species Macaca mulatta and mention the gene name mir-181a-1. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 105
These data suggest that the downregulation of miR-181a we observed with age in serum correlates with an upregulation of pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. [score:10]
In addition, the expression levels of these miRNAs are fairly consistent between monkeys and humans in that miR-181a-5p is highly expressed, while other miRNAs are expressed at lower levels. [score:7]
Given that the presence of low-grade systemic chronic inflammation is associated with the development and progression of age-related diseases and conditions, it is interesting to speculate that miR-151a-3p, miR-181a-5p and miR-1248 may be important for regulating inflammatory processes and inhibiting inflammation -associated aging in young individuals. [score:7]
Although in most instances miR-181a-1 attenuates inflammatory responses, in some cases miR-181 family members are upregulated by inflammatory signals and have been reported to be pro-inflammatory, which may explain its reported dual roles as a tumor suppressor-miR or onco-miR in different types of cancers. [score:6]
To understand more thoroughly how these miRNAs may contribute to the aging process, we examined several mRNA targets of miR-151a-3p, miR-181a-5p and miR-1248 as predicted using TargetScan 6.2. [score:5]
miR-181a, miR-1248 and miR-3607 were significantly downregulated in serum from old individuals using Poisson regression (miR-181a-1 P=0.03, miR-3607 P=0.01, miR-1248 P=4.9×10 [−9]). [score:4]
The regulatory role that miR-181a-1 plays in hematopoiesis may also help to explain the high expression we observed in both human and monkey serum. [score:4]
In agreement with this idea, miR-181a has been shown to be upregulated in centenarians [16, 17], who exemplify exceptional longevity. [score:4]
These data suggest that miR-181a-1 expression may be an important age-related factor that regulates inflammatory responses with age. [score:4]
Consistent with this idea, we found that miR-1248 regulates genes involved in various cytokine pathways and specifically modulates the pro-inflammatory cytokines IL-6 and IL-8. In addition, accumulating data indicate that miR-181a-1 targets several inflammatory cytokines including the mRNAs that encode IL-1β, IL-1α, IL-6, IL-8, IL-10, TNFα, TGFβ, FGF2, HMGB1 and LIF [27- 29]. [score:4]
Interestingly, we found that miR-181a-5p expression decreases with age in rhesus monkeys, but increases in extremely old monkeys (n=3, mean age=39.7 years; data not shown). [score:3]
Consistent with our sequencing data, we found that miR-181a-5p was by far the most highly expressed serum miRNA among the miRNAs that we analyzed (Figure 3), confirming that our sequencing data gave a quantitative assessment of miRNA abundance. [score:3]
We found that miR-181a expression was significantly negatively correlated with the pro-inflammatory cytokines IL-6 and TNFα and positively correlated with the anti-inflammatory cytokine TGFβ (Table 2). [score:3]
Further suggesting that miR-181a expression may be a potential biomarker of healthy aging in humans and in non-human primates. [score:3]
We identified 115, 626 and 265 mRNAs that were predicted to be targeted by miR-151a-3p, miR-181a and miR-1248, respectively (Figure 5A). [score:3]
Based on our sequencing data, we found differential expression of three miRNAs: miR-181a-1, miR-1248 and miR-3607 with human age. [score:3]
Here we found that the levels of pro-inflammatory cytokines IL-6 and TNFα negatively correlated with miR-181a-5p expression and the levels of anti-inflammatory cytokines TGFβ and IL-10 positively correlated with miR-181a-5p. [score:3]
This analysis suggests that miR-151a-3p, miR-181a-5p and miR-1248 may target similar, yet distinct signaling pathways important for the aging process. [score:3]
Since the top network mediator for miR-181a is TNFα and because this miRNA has been shown to target several other inflammatory markers [27- 29], we hypothesized that the decline in miR-181a with age that we found may be a cause of the increased inflammation that occurs with old age. [score:3]
Other inflammatory miR-181a targets, IL-1α, IL-1β, IL-8 and LIF, were found to be low or undetectable in the serum from our young and old individuals. [score:3]
It is interesting to note that in human PBMCs and in the mouse brain miR-181a-1 expression is decreased with age [13, 14, 17, 34] and may also play a role in senescence [35], suggesting that miR-181a-1 may be important for healthy aging. [score:3]
It should also be noted that miR-181 is an important regulator of hematopoiesis, therefore, decreased miR-181a-1 may impact hematopoietic lineage development during aging [36]. [score:3]
In our validation experiments in the larger cohort, we found a significant decrease in expression of miR-151a-3p, miR-181a-5p, and miR-1248. [score:3]
Therefore, we examined several inflammatory markers that have been reported to be targeted by miR-181a in serum from the young and old individuals of our cohort. [score:3]
Demographic information for this validation cohort is in Table 1. Three of the miRNAs we analyzed, miR-151a, miR-181a-1 and miR-3607, are precursors that can be processed into two mature miRNAs according to miRBase (miR-151a-3p and −5p, miR-181a-3p and −5p and miR-3607-3p and −5p). [score:1]
miR-181a-5p and miR-1248 were significantly decreased in old individuals (Figure 3). [score:1]
Figure 1 (A) Frequency of miRNA reads per individual using small RNA NGS from 11 young (~30 yr) and 11 old (~64 yr) individuals for miR-181a-1, miR-3607, miR-1248, miR-151a and miR-151b. [score:1]
Three serum miRNAs were significantly decreased in old individuals: miR-151a-3p, miR-181a-5p and miR-1248. [score:1]
We found significantly lower levels of miR-151-5p and miR-1248 and a close to significant (p=0.09) decrease in miR-181a-5p levels with monkey age (Figure 4). [score:1]
Although the anti-inflammatory cytokine IL-10 was only detected in 6 participants (3 young and 3 old), it was highly correlated with miR-181a-5p levels (R=0.84, P<0.01). [score:1]
Importantly, miR-181a-1, miR-1248 and miR-3607 were significantly lower in old individuals (Figure 1A). [score:1]
Lower levels of miR-151a-5p, miR-181a-1-3p, miR-3607-3p and miR-3607-5p were also observed in old individuals, though not significantly. [score:1]
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2
[+] score: 29
While several miRNAs were upregulated in old muscle tissues, a few were downregulated, including miR-181a (Table 1), in agreement with the lower expression of miR-181a in skeletal muscle tissues of old mice [37]. [score:9]
Furthermore, miR-181 has been found to be anti-inflammatory by suppressing the expression of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, and IL-8 [38, 39]. [score:5]
Additionally, miR-181a may potentially regulate the type IIA activin receptor, which inhibits proliferation of skeletal muscle-derived progenitors through Smad 2/3 phosphorylation [42]. [score:4]
This observation suggests that downregulation of miR-181a in old muscle tissues may restrict satellite cell proliferation and thus reduce the ability to replace damaged muscle. [score:4]
Thus, we propose that downregulation of miR-181a may be related to increased inflammation in the elderly. [score:4]
In aged human subjects, reduced miR-181a was found to be associated with impaired T-cell receptor sensitivity by increasing the activity of dual specificity phosphatase 6 (DUSP6) [41]. [score:1]
However, CR rescued the age-related decline of miR-181a (Fig. 2), which may reflect enhanced muscle mass, strength, and proliferation, as well as reduced inflammation in these animals. [score:1]
It is important to note that an age -associated decrease in miR-181a was also observed in mouse brain but the impact of miR-181a on brain aging is unknown [40]. [score:1]
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3
[+] score: 3
Additionally we have shown that these changes in mRNA and protein levels of STAT3 are mediated by increased expression of microRNAs miR-181 and miR-22 and resulted in ethanol dependent disruption of growth factors (VEGF, HGF) and inflammatory cytokine production (G-CSF) in PBMC following phorbol myristate acetate(PMA)/ ionomycin stimulation[15]. [score:3]
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