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21 publications mentioning rno-mir-139

Open access articles that are associated with the species Rattus norvegicus and mention the gene name mir-139. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 320
Other miRNAs from this paper: mmu-mir-139
Inhibition of c-Jun activation suppresses miR-139-5p knockdown -induced cardiac hypertrophyAs the expression of c-Jun was found to be regulated by miR-139-5p in NRCMs, we proposed that the up-regulation of c-Jun might be required in miR-139-5p deprivation -induced cardiac hypertrophy. [score:12]
miR-139-5p down-regulates c-Jun expression in ISO -induced cardiac hypertrophymiRs specifically bind to the 3′-UTR of its target mRNAs to regulate their expression. [score:11]
The expression of IGF-1R was down-regulated by miR-139-5p in NRCMs, although ISO alone slightly down-regulated IGF-1R expression (Figure 4A,B). [score:11]
miR-139-5p also inhibits the expression of IGF-1R in cells both under basal and ISO-stimulated conditions, indicating that the down-regulation of IGF-1R and inhibition of Akt might be involved in preventing cardiac hypertrophy. [score:10]
We observed that miR-139-5p indeed down-regulated β-catenin expression under basal conditions, but it failed to inhibit Wnt1 or β-catenin expression in response to ISO stimulation (Figure 4A,B). [score:10]
Interestingly, miR-139-5p overexpression inhibited the ISO -induced up-regulation of c-Jun expression (Figure 4A,B). [score:10]
In our study, we observed that miR-139-5p indeed down-regulated β-catenin expression under basal conditions; however, it failed to antagonize the ISO -induced up-regulation of β-catenin in NRCMs. [score:9]
miR-139-5p is down-regulated in hypertrophic heartsTo validate whether miR-139-5p is down-regulated in hypertrophic hearts, we detected its expression in left ventricular tissues from 16 HCM patients and 8 healthy donors. [score:9]
Consistently, the expression of ANP and BNP was up-regulated by ISO treatment by 2.11- and 7.68-fold, respectively (Figure 3C), whereas the transfection of NRCMs with the miR-139-5p mimic attenuated the ISO -induced increase in ANP and BNP expression (Figure 3C). [score:8]
Consistently, the expression of miR-139-5p in the hearts of TAC-operated mice was significantly down-regulated compared with that in sham-operated mice, indicating that miR-139-5p is down-regulated in hypertrophic hearts (P<0.01, power: 0.765) (Figure 1B). [score:8]
As expected, the increase in cell surface area and the up-regulation of ANP expression induced by miR-139-5p deprivation were restored by c-Jun knockdown (Figure 4G–I). [score:7]
As the expression of c-Jun was found to be regulated by miR-139-5p in NRCMs, we proposed that the up-regulation of c-Jun might be required in miR-139-5p deprivation -induced cardiac hypertrophy. [score:7]
Moreover, the expression of miR-139-5p was down-regulated in the hearts of TAC-operated mice, and knockdown of miR-139-5p in NRCMs induced cardiomyocyte enlargement. [score:7]
The knockdown of miR-139-5p expression in NRCMs significantly increase c-Jun levels, whereas the knockdown of c-Jun expression prevented this increase (Figure 4E,F). [score:7]
To validate whether miR-139-5p is down-regulated in hypertrophic hearts, we detected its expression in left ventricular tissues from 16 HCM patients and 8 healthy donors. [score:6]
miR-139-5p down-regulates c-Jun expression in ISO -induced cardiac hypertrophy. [score:6]
Inhibition of c-Jun activation suppresses miR-139-5p knockdown -induced cardiac hypertrophy. [score:6]
We found that the expression of miR-139-5p in left ventricular tissues of HCM patients was down-regulated to 57.6% of that in the healthy donors (P<0.05, power: 0.505) (Figure 1A). [score:6]
miR-139-5p attenuates cardiac hypertrophy possibly through the down-regulation of c-Jun expression in vitro. [score:6]
Figure 1 miR-139-5p is down-regulated in hypertrophic hearts(A) Expression of miR-139-5p in 16 HCM patients and 8 healthy donors (Control). [score:6]
These results indicated that miR-139-5p inhibits the expression of c-Jun in cardiomyocytes and thus might play an important role in the regulation of cardiac hypertrophy. [score:6]
The knockdown of miR-139-5p induced a 2.06-fold increase in ANP expression (P<0.05); however, the expression of BNP was unchanged (Figure 2C). [score:6]
The knockdown of miR-139-5p expression in NRCMs induced cardiac hypertrophy, whereas the exogenous overexpression of miR-139-5p antagonized ISO -induced cardiac hypertrophy. [score:6]
Figure 4 miR-139-5p targets c-Jun expression in cardiomyocytes(A– D) NRCMs were treated as indicated. [score:5]
org/vert_71/), an online tool for predicting miR target genes, we identified c-Jun, IGF-1R, MyoCD, Wnt1, and β-catenin as candidate target genes of miR-139-5p. [score:5]
In the present study, we observed that c-Jun expression was strongly induced by ISO-treatment, whereas miR-139-5p inhibited this increase. [score:5]
miR-139-5p targets c-Jun expression in cardiomyocytes. [score:5]
In addition, we found that the predicted MyoCD was not a target of miR-139-5p in NRCMs, as its expression was not altered under basal or ISO-stimulated conditions. [score:5]
In colitis -associated tumorigenesis, miR-139-5p inhibits the cross-talk between the PI3K/Akt and Wnt pathways by targetting IGF-1R [35]. [score:5]
The expression of Wnt1 was not altered by miR-139-5p overexpression in NRCMs. [score:5]
Consistently, the knockdown of c-Jun expression significantly attenuated miR-139-5p deprivation -induced cardiac hypertrophy. [score:4]
Knockdown of miR-139-5p expression induces cardiac hypertrophy. [score:4]
The levels of miR-139-5p were down-regulated to 25.4% of that in control NRCMs at 48 h post transfection (Figure 2A). [score:4]
Figure 2Knockdown of miR-139-5p expression induces cardiac hypertrophy. [score:4]
Our data indicated that the down-regulation of c-Jun is indispensable for the anti-hypertrophic effects of miR-139-5p in cardiomyocytes. [score:4]
By using microarray analysis, we found that miR-139-5p was significantly down-regulated in the left ventricular tissues of HCM patients. [score:4]
In the present study, we reported that miR-139-5p was down-regulated in heart tissues of HCM patients. [score:4]
Mi et al. [20] reported that Wnt1 and β-catenin were directly targetted by miR-139-5p in C2C12 cells. [score:4]
miR-139-5p is required for maintaining normal cell size in cardiomyocytesTo investigate the role of miR-139-5p in cardiac hypertrophy, we knocked down its expression in NRCMs by transfecting a specific miR inhibitor. [score:4]
miR-139-5p is down-regulated in hypertrophic hearts. [score:4]
We transfected NRCMs with the miR-139-5p mimic for 48 h and found that the levels of c-Jun, IGF-1R, and β-catenin were all down-regulated, whereas the levels of MyoCD and Wnt1 were unaffected (Figure 4A,B). [score:4]
To investigate the role of miR-139-5p in cardiac hypertrophy, we knocked down its expression in NRCMs by transfecting a specific miR inhibitor. [score:4]
Overexpression of miR-139-5p attenuates ISO -induced cardiac hypertrophySince miR-139-5p participates in the regulation of cell size in cardiomyocytes, we wanted to explore whether the exogenous administration of miR-139-5p is able to antagonize cardiac hypertrophy. [score:4]
All mice were killed at 4 weeks post operation, and the hearts were harvested for miR-139-5p expression analysis. [score:3]
Overexpression of miR-139-5p attenuates ISO -induced cardiac hypertrophy. [score:3]
We observed that miR-139-5p overexpression attenuated ISO -induced cardiac hypertrophy, which indicated that miR-139-5p plays an antihypertrophic role in the heart. [score:3]
The expression of miR-139-5p was determined using the following primers: forward, 5′-ACACTCCAGCTGGGTCTACAGTGCACGTGTC-3′ and reverse, 5′-TGGTGTCGTGGAGTCG-3′, and normalized to U6 expression determined with the following primers: forward, 5′-CTCGCTTCGGCAGCACA-3′ and reverse, 5′-AACGCTTCACGAATTTGCGT-3′. [score:3]
These findings provide evidences that the miR-139-5p/c-Jun axis is a novel target for the prevention and treatment for cardiac remo deling. [score:3]
The future study will focus on the mechanism of miR-139-5p expression and its association with c-Jun. [score:3]
NRCMs were transiently transfected with miR-139-5p mimics or inhibitors (GenePharma, Suzhou, China) at a final concentration of 100 nM. [score:3]
Figure 3Overexpression of miR-139-5p attenuates ISO -induced cardiac hypertrophy(A– C) NRCMs were transfected with the miR-139-5p mimic or scrambled control small RNAs for 48 h, followed by ISO treatment for 24 h. Intracellular F-actin and nuclei were stained with Texas Red-Phalloidin and DAPI, respectively. [score:3]
As expected, miR-139-5p suppressed ISO -induced hyperphosphorylation of Akt in NRCMs, indicating that the IGF-1R/Akt pathway might also contribute to the antihypertrophic effects of miR-139-5p (Figure 4C,D). [score:3]
Our results indicated that overexpression of miR-139-5p in NRCMs antagonizes ISO -induced activation of Akt. [score:3]
To analyze the expression of miR-139-5p, a specific primer containing a stem loop structure was used for cDNA synthesis with a cDNA synthesis kit (Takara, Dalian, China): 5′-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACTGGAGA-3′. [score:2]
Since miR-139-5p participates in the regulation of cell size in cardiomyocytes, we wanted to explore whether the exogenous administration of miR-139-5p is able to antagonize cardiac hypertrophy. [score:2]
Wnt1/β-catenin has been reported to be regulated by miR-139-5p [20]. [score:2]
To investigate this aspect, we knocked down c-Jun expression by transfecting c-Jun-specific siRNAs into miR-139-5p-deprived NRCMs. [score:2]
In contrast, the knockdown of endogenous miR-139-5p increased the level of c-Jun (Figure 4E,F). [score:2]
Our data indicated that the exogenous delivery of the miR-139-5p mimic to the heart might be a potential therapeutic strategy for pathological cardiac hypertrophy. [score:1]
These data indicated that the Wnt1/β-catenin pathway might not be associated with the antihypertrophic effects of miR-139-5p. [score:1]
These data indicated that miR-139-5p is indispensable in normal cardiomyocytes. [score:1]
These data indicated that miR-139-5p attenuates ISO -induced cardiac hypertrophy in vitro. [score:1]
miR-139-5p is required for maintaining normal cell size in cardiomyocytes. [score:1]
In addition, miR-139-5p did not affect cell surface area or ANP/BNP levels under basal conditions (Figure 3A–C). [score:1]
These results indicated that c-Jun is indispensable in miR-139-5p deprivation -mediated cardiac hypertrophy in vitro. [score:1]
Pre-transfection of NRCMs with the miR-139-5p mimic for 48 h attenuated ISO -induced cellular enlargement (Figure 3A,B). [score:1]
These findings indicated that miR-139-5p acts an anti-hypertrophic miR in the heart. [score:1]
The miR-139-5p/c-Jun axis has been reported to form a feedback loop in human gastric cancer cells [33]. [score:1]
These results indicated that miR-139-5p is required to maintain normal cell size in cardiomyocytes. [score:1]
Taken together, our study highlights that miR-139-5p is a novel antihypertrophic miR in cardiomyocytes. [score:1]
We found that the cell surface area was significantly increased in miR-139-5p-deprived NRCMs (Figure 2B). [score:1]
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2
[+] score: 225
Other miRNAs from this paper: rno-mir-133a, rno-mir-1
Targeting of ROCK2 by miRNA-139-5p was further verified by our current IPA as shown in Fig.   2. In addition, present data using qPCR, WB, ICC, and functional data in the IAS tone, and direct contractility assays using MTC, following overexpression and knockdown of miRNA-139-p suggest that miRNA-139-5p negatively regulates the IAS tone via ROCK2. [score:7]
Among nine differentially expressed miRNAs, miRNA-139-5p is the most differentially expressed, with ~4-fold higher expression in the ASM vs. [score:7]
Collectively, these data examining the effect in the basal and ROCK-activated states, and kinetic analyses of the IAS tone suggest that miRNA-139-5p by suppressing ROCK2 expression produces inhibitory effects in the basal tone and on the fibroelastic properties of the smooth muscle. [score:7]
The lower portion of this panel provides the quantitative data showing that miRNA-139-5p significantly (* p < 0.05) downregulates, while anti-miRNA-139-5p causes significant (* p < 0.05) upregulation of p-MYPT1 and p-MLC [20]. [score:7]
It is noteworthy that, in contrast with the regulation of ROCK2, miRNA-139-5p caused no significant decrease in the expression of ROCK1 (p > 0.05; n = 4), suggesting the specificity of miRNA-139-5p targeting ROCK2. [score:6]
Our immunoblot and ICC analysis also revealed downregulation of RhoA, ROCK2, pMYPT1, and p-MLC [20] proteins in miRNA-139 -transfected cells, speculatively via targeting ROCK2. [score:6]
Among different miRNAs, only nine miRNAs met these criteria, and further scrutiny revealed that miRNA-139-5p was the most differentially expressed with highest expression in the ASM > RSM > IAS SMCs. [score:5]
Of further importance, miRNA-139-5p has been shown to be a potential tumor suppressor in humans by targeting ROCK2 35, 36, 44, 45. [score:5]
This comparison revealed a gradient of expression of miRNA-139-5p with ASM > RSM > IAS, with miRNA-139-5p expression negatively correlating with the known levels of tone in the tissues. [score:5]
The effect of miRNA-139-5p overexpression was found to be selective given anti-miRNA-139-5p significantly (*p < 0.05; Fig.   5A) reversed the inhibitory effect of miRNA-139-5p on the IAS tone. [score:5]
The analysis shows that human ROCK2 is one of the direct targets of miR-139-5p as it has a direct miR-139-5p binding site at its 3′UTR. [score:5]
The current study examining the phenotypic smooth muscles and cells from IAS (purely tonic), RSM (semi tonic) and the ASM (purely phasic), demonstrate that the expression levels of miRNA-139-5p correlate inversely with those of tone and ROCK2 expression. [score:5]
Conversely, anti-miRNA-139-5p by itself causes significant upregulation of RhoA and ROCK2 (* p < 0.05). [score:4]
Figure 2 Ingenuity pathway analysis (IPA) showing ROCK2 as one of the direct targets of miRNA-139-5p. [score:4]
Earlier studies using cancer cell lines 35, 36, 44, 45 have shown that miRNA-139-5p targets ROCK2 directly in humans. [score:4]
The lower portion of the panel provides the corresponding quantitative data showing that miRNA-139-5p causes significant (* p < 0.05) downregulation of RhoA and ROCK2 without any significant (p > 0.05) effect on the levels of ROCK1. [score:4]
These studies employed the approaches of overexpression and knockdown of miRNA-139-5p using selective oligomer and anti-miRNA-139-5p, respectively. [score:4]
To determine the effect of miRNA-139-5p on smooth muscle function, we overexpressed or knocked down miRNA-139-5p in IAS smooth muscle strips (for force experiments), and SMCs (for MTC experiments monitoring direct contraction assay of SMCs) by transfecting them with synthetic miRNA-139-5p and anti-miRNA-139-5p, respectively. [score:4]
In addition, these data for the first time show that miRNA-139-5p negatively regulates the tonic smooth muscle function via suppression of RhoA/ROCK2. [score:4]
According to previously published studies, one of the direct targets of miRNA-139-5p in humans was identified to be ROCK2 35, 36, 44, 45. [score:4]
Effect of miRNA-139-5p transfection on the speed of relaxation with 0 Ca [2+] and of redevelopment of IAS tone following replenishment with normal Ca [2+]Since RhoA/ROCK plays an important role in the development of IAS tone and in the fibroelastic properties 11, 14, 18, 41, 46, it was considered important to determine whether miRNA-139-5p by suppressing ROCK2 affects the speed of IAS relaxation and genesis of IAS tone following 0 Ca [2+], and Ca [2+] replenishment, respectively. [score:4]
miRNA microarray data was subjected to ingenuity pathway analysis (IPA) and various validated targets of miR-139-5p from the literature were plotted as an Interactome. [score:3]
Differential expression of miRNA-139-5p identified above via miRNA microarray and qPCR data (Fig.   1) was further validated using immunoblot and immunofluorescence analyses for Rho kinase and its downstream signaling molecules. [score:3]
Of equal significance, in contrast with the effect of miRNA-139-5p, reducing expression of miRNA-139-5p using anti-miRNA-139-5p had the opposite effect, causing an increase in the IAS tone. [score:3]
Effect of miRNA-139-5p overexpression on RhoA/ROCK pathway. [score:3]
In summary, our studies suggest that miRNA-139-5p plays a significant role in the functional phenotypic smooth muscles by repressing RhoA/ROCK pathway in the SMCs, and that its low expression in the IAS may contribute to the basal tone. [score:3]
miRNA-139-5p targets in SMCs as shown by IPA. [score:3]
Possible targets of miRNA-139-5p were identified by IPA analysis as described previously 26, 29 (Fig.   2). [score:3]
Since RhoA/ROCK plays an important role in the development of IAS tone and in the fibroelastic properties 11, 14, 18, 41, 46, it was considered important to determine whether miRNA-139-5p by suppressing ROCK2 affects the speed of IAS relaxation and genesis of IAS tone following 0 Ca [2+], and Ca [2+] replenishment, respectively. [score:3]
qPCR studies validated this trend of miRNA-139-5p for its significantly differential expression (*p < 0.05; n = 4; Fig.   1C). [score:3]
Most strikingly, these SMCs transfected with anti-miRNA-139-5p showed faster and greater cell stiffening responses to 100 nM U46619, and this single-cell contraction was inhibited by miRNA-139-5p (Fig.   7B). [score:3]
Since present studies did not determine a direct target site of miR-139-5p in rat ROCK2 UTR previously established in humans, an indirect effect via some other intermediary proteins cannot be ruled out and deserves further investigation. [score:3]
Important insight into this question was provided by miRNA microarray analyses that identified miRNA-139–5p to be one of the most differentially expressed miRNAs in three phenotypic smooth muscles with a gradient of negative correlation with the levels of tone. [score:3]
In addition, involvement of other intermediary pathways or targets of miRNA-139-5p such as TGF-β, Wnt, MAPK, and PI3K reported to inhibit RhoA/ROCK [35] and microRNA -mediated G protein-coupled receptors (GPCR) crosstalk [52], require further investigations. [score:3]
Further literature and network analysis revealed that in different systems, miRNA-139-5p targets ROCK2 35, 36. [score:3]
Data suggest that higher levels of miRNA-139-5p in the IAS attenuate ROCK2 expression, which in turn leads to activation of MLCP (via decrease in p-MYPT1), and decrease in p-MLC [20] and basal tone. [score:3]
Data revealed that miRNA-139-5p inhibited the velocity (shown by the rightward shift in the time-course curve) of fast contraction, and the maximal contraction produced by U46619 (*p < 0.05; n = 4; Fig.   5C). [score:3]
Western blots comparing the expression levels of RhoA, ROCK1, and ROCK2 before and after miRNA-139-5p, anti-miRNA-139-5p alone, and following miRNA-139-5p + anti-miRNA-139-5p. [score:3]
Western blots comparing the expression levels of p-MYPT1and p-MLC [20], before and after miRNA-139-5p, anti-miRNA-139-5p alone, and following miRNA-139-5p + anti-miRNA-139-5p. [score:3]
Among nine miRNAs, we observed a graded and most differential decrease in miRNA-139-5p expression ASM > RSM > IAS. [score:3]
Moreover, anti-miRNA-139-5p expression itself caused a significant leftward shift in the U46619 CRC (*p < 0.05; n = 4; Fig.   5B). [score:3]
Transfection of rat IAS SMCs with miRNA-139-5p oligonucleotide (for 72 h) caused a significant decrease in the basal expression levels of RhoA/ROCK2, p-MYPT1, and p-MLC [20] as determined via immunoblot (*p < 0.05; n = 4; Fig.   3A,B). [score:3]
Figure 3Effect of miRNA-139-5p overexpression on RhoA/ROCK machinery in IAS SMCs. [score:3]
In addition, since both basal IAS tone 11– 14, 16, 18 and response to U46619 29, 47, which are critically dependent on RhoA/ROCK activation, were attenuated by ROCK2 siRNA, suggest that miRNA-139-5p exerts its effects via ROCK2 suppression. [score:3]
Data revealed that miRNA-139-5p causes a significant decrease in the speed of both relaxation following 0 Ca [2+] (*p < 0.05; n = 4; Fig.   6A) and of redevelopment of the tone following Ca [2+] replenishment (*p < 0.05; n = 4; Fig.   6B). [score:2]
Mi L MicroRNA-139-5p suppresses 3T3-L1 preadipocyte differentiation through Notch and IRS1/PI3K/Akt insulin signaling pathwaysJ Cell Biochem. [score:2]
We subsequently performed miRNA-139-5p gain- and loss- of function studies to define the role of miRNA-139-5p in the ROCK2 -dependent regulation of smooth muscle phenotype. [score:2]
Effect of miRNA-139-5p transfection on the speed of relaxation with 0 Ca [2+] and of redevelopment of IAS tone following replenishment with normal Ca [2+]. [score:2]
Those data are in agreement with our hypothesis that miRNA-139-5p regulates specific functioning of tonic vs. [score:2]
These data further support the concept that miRNA-139-5p regulates the IAS tone and smooth muscle phenotype differentiation via RhoA/ROCK. [score:2]
Consistent with the data in the smooth muscle strips, MTC data demonstrate that transfection of human IAS SMCs with ROCK2 siRNA and miRNA-139-5p decreased baseline cell stiffness (basal tone) (Fig.   7A). [score:1]
Anti-miRNA-139-5p significantly reversed this effect of miRNA-139-5p (*p < 0.05; n = 4). [score:1]
Consistent with the rat smooth muscle data, anti-miRNA-139-5p causes faster and greater cell stiffening in response to U46619. [score:1]
miRNA-139-5p significantly (* p < 0.05) decreases the rates of relaxation and of recovery of the IAS tone which are significantly reversed by anti-miRNA-139-5p pre-treatment (* p < 0.05; n = 6–8). [score:1]
The blockade of these effects by anti-miRNA-139-5p demonstrates the selectivity of actions of miRNA-139-5p. [score:1]
Increased basal tone in response to anti-miRNA-139-5p was attenuated with co-transfection with miRNA-139-5p. [score:1]
Figure 5Effect of miRNA- and anti-miRNA-139-5p. [score:1]
Effect of miRNA-139-5p and anti-miRNA-139-5p on ROCK activator U46619 -induced increase in IAS tone. [score:1]
Figure 7MTC data showing the effect of miRNA- and anti-miRNA-139-5p. [score:1]
The main objective of the present study was to determine the role of miRNA-139-5p in the IAS tone in relation to ROCK2. [score:1]
Conversely, anti-miRNA-139-5p significantly (* p < 0.05) increases the maximal effect and produces left-ward shift in time-course of U46619 -induced contraction. [score:1]
Figure 4Immunocytochemistry data before and after miRNA-139-5p. [score:1]
Present data suggest an important role of miRNA-139-5p in determining the levels of smooth muscle tone and phenotype differentiation. [score:1]
These data show the specificity of both miRNA and anti-miRNA-139-5p. [score:1]
Both of these miRNA-139-5p-affected events were significantly reversed by anti-miRNA-139-5p (*p < 0.05). [score:1]
The smooth muscle transfection experiments with miRNA-139-5p reveal a decrease in the basal tone, and attenuation of ROCK activator U46619 -induced an increase in the tone. [score:1]
Figure 6Effect of miRNA- and anti-miRNA-139-5p on IAS kinetics. [score:1]
The rightward shift in the velocity following miRNA-139-5p, and its reversal following anti-miRNA was shown by the regression lines. [score:1]
Additional experiments show that miRNA-139-5p decreases the speeds of relaxation and recovery to the basal IAS tone following 0 Ca [2+] and normal Ca [2+] respectively. [score:1]
The above described effect of miRNA-139-5p is significantly (* p < 0.05) attenuated by the pre-transfection of the smooth muscles with anti-miRNA-139-5p. [score:1]
Considering the role of Rho kinase in maintaining basal IAS SM tone 11, 14, 18, we investigated whether the decreased expression of ROCK2 by miRNA-139-5p is responsible for the changes in the basal tone. [score:1]
Collectively, these data suggest an important role of miRNA-139-5p in the genesis of basal tone in the IAS and lack of tone in the purely phasic smooth muscles such as the ASM. [score:1]
Strips were transfected with miRNA-139-5p as per [29]. [score:1]
Of added significance the anti-miRNA-139-5p caused an augmentation in basal tone and its increase following U46619 provide further credence to the hypothesis that miRNA-139-5p plays an important role in the maintenance of tonicity in the IAS via RhoA/ROCK signaling. [score:1]
Effect of miRNA-139-5p on basal and U46619 -induced stiffness using direct IAS SMC contractility assay via MTC. [score:1]
Influence of miRNA-139-5p and anti-miRNA-139-5p on kinetics and amplitude of peak increase in IAS tone by U46619. [score:1]
Effect of miRNA-139-5p and anti-miRNA-139-5p on the basal tone. [score:1]
Transfection of miRNA and anti-miRNA-139-5p. [score:1]
In vitro transfections of locked nucleic acid (LNA) miRNA-139-5p and anti-miRNA-139-5p (Exiqon, MA) in SMCs and tissue strips were performed by using Hiperfect transfection reagent from Qiagen. [score:1]
Data showed that transfection of IAS muscle strips with miRNA-139-5p (100 nM for 48 h) significantly decreased (33 ± 7%; p < 0.05; n = 4; Fig.   5A) basal tone. [score:1]
Transfection of the IAS smooth muscle strips with miRNA-139-5p caused a significant rightward shift in the U46619 CRC (*p < 0.05; n = 4; Fig.   5B). [score:1]
For these experiments, we determined the time-course effect of miRNA and anti-miRNA-139-5p, alone and in combination, on U46619 (1 µM) -induced increase in the IAS tone over a period of 20 min. [score:1]
miRNA-139-5p encoded within the second intron of the phosphodiesterase 2 A (PDE2A) gene has been shown to be located on chromosome 11 [35]. [score:1]
Figure  3C depicts a mo del showing miRNA-139-5p associated attenuation of RhoA/ROCK2 signaling leading to decreases in p-MYPT1 and p-MLC [20]. [score:1]
Importantly, ant-miRNA-139-5p had an effect opposite to that of miRNA-139-5p, i. e. it caused a significant increase in the amplitude of maximal contraction with a leftward shift in the U46619 response kinetics during initial phase of contraction (*p < 0.05; n = 4). [score:1]
Conversely, transfection of human IAS SMCs with anti-miRNA-139-5p increased basal tone, which was attenuated by co-transfection with miRNA-139-5p (Fig.   7A). [score:1]
SMCs transfected with ROCK2 siRNA and miRNA-139-p showed decreases in baseline cell stiffness (basal tone) while cells transfected with anti-miRNA-139-5p showed increases in basal tone. [score:1]
Concentration-response curves (CRC) for thromboxane A [2] analog U46619 (1 nM to 1 µM), and single concentration contractile response for U46619 (1 µM) were examined in the muscle strips pretreated for 48 h with scrambled miRNA (control), and miRNA-139-5p before and after anti-miRNA-139-5p. [score:1]
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3
[+] score: 185
In conclusion, our study confirmed that 1) elevated levels of miR-139-5p in the pancreatic tissues of diabetic rats can suppress IRS1 gene expression to promote cell apoptosis, and 2) liraglutide has anti-apoptotic effects by downregulating miR-139-5p levels and upregulating IRS1 gene expression. [score:13]
Our findings suggest a new pathway that links GLP-1 to inhibition of β-cell apoptosis by downregulating the targeting of miR-139-5p to IRS1. [score:8]
MiR-139-5p, a recognized tumor-suppressing miRNA, has been shown to be down-regulated in a variety of cancers [10, 11]. [score:6]
These data suggest that rno-miR-139-5p may specifically regulate IRS1 expression by targeting ACTGTAG at the 3′-UTR. [score:6]
Therefore, GLP-1 may play an important role in biology by downregulating miR-139, which introduces a new research direction for the treatment of diabetes using GLP-1. Whether liraglutide inhibited miR-139 via pathways such as cAMP/protein kinase A -dependent pathway need to be investigated in future studies. [score:5]
In INS-1 cells exposed to liraglutide, miR-139-5p expression was markedly downregulated compared with control cells exposed to palmitic acid (palmitic acid group: 4.3 ± 0.97 vs. [score:5]
We found that palmitic acid can increase the expression of miR-139-5p and reduce IRS1 expression at both the mRNA and protein level. [score:5]
These data indicate that transfection with miR-139-5p mimics can suppress IRS1 expression in INS-1 cells. [score:5]
It demonstrated that miR-139-5p inhibited the IRS1 expression by interacting with the 3’-UTR of IRS1. [score:5]
Additionally, transfection with miR-139-5p mimics suppressed IRS1 expression in INS-1 cells. [score:5]
Second, overexpression of miR-139-5p enhanced INS-1 cell apoptosis, associated with caspase-3 activity and Bcl-2 expression. [score:5]
We performed a dual-luciferase reporter assay and found that rno-miR-139-5p may specifically regulate IRS1 expression by targeting ACTGTAG at the 3′UTR. [score:5]
These findings suggest that increases in miR-139-5p expression increase β-cell apoptosis by targeting IRS1. [score:5]
Third, we found that miR-139-5p is a key intermediary that links GLP-1 signaling with suppression of IRS1 expression. [score:5]
Mechanistically, we demonstrated that miR-139-5p specifically suppressed IRS1 expression. [score:5]
MiR-139-5p specifically suppresses IRS1 expression. [score:4]
Although miR-139-5p has been described in a limited number of studies as a potential tumor suppressor miRNA [21, 22], little is known about the function or regulation of miR-139-5p in β-cells. [score:4]
Among these, miR-139-5p expression increased by 4.1-fold in the DM group, and it decreased by over 90% following liraglutide treatment (Table 1). [score:3]
We next studied the effects of transfection with miR-139-5p mimics on IRS1 expression level in INS-1 cells. [score:3]
Overexpression of miR-139-5p enhanced INS-1 cell apoptosis by analysis with annexin V and PI staining (n = 3,*p<0.05). [score:3]
In contrast with the DM group, the expression levels of miR-139-5p decreased after liraglutide treatment (DM group: 3.4 ± 0.68 vs. [score:3]
GLP-1 and miR-139-5p both target cells apoptosis, but their potential links were unclear. [score:3]
After a search of bioinformatics websites such as TargetScan, we found that miR-139-5p was complementary to the sequence, ACTGTAG, on the 3′-UTR of IRS1. [score:3]
Overexpression of miR-139-5p promotes lung cancer cell apoptosis, which is associated with caspase-3 activation [12]. [score:3]
The overexpression of miR-139-5p increased INS-1 cell apoptosis. [score:3]
Moreover, we sought to explore the target genes of miR-139-5p following liraglutide treatment. [score:3]
0173576.g007 Fig 7 Cells were divided into control, PA and PA+Lira group, which respectively treated with vehicle, palmitic acid (0.5nmol/L) or palmitic acid (0.5mmol/L) + liraglutide (100nmol/L) for 48 h. Overexpression of miR-139-5p increased apoptosis of INS-1 cells (Fig 8). [score:3]
The findings reported in this manuscript reveal that expression of miR-139-5p decreased after GLP-1 treatment in both cellular and animal mo dels. [score:3]
0173576.g007 Fig 7 Cells were divided into control, PA and PA+Lira group, which respectively treated with vehicle, palmitic acid (0.5nmol/L) or palmitic acid (0.5mmol/L) + liraglutide (100nmol/L) for 48 h. Overexpression of miR-139-5p increased apoptosis of INS-1 cells (Fig 8). [score:3]
Our study suggest that miR-139-5p may promot apoptosis by targeting BCL2 in INS-1 cells. [score:3]
The expression of miR-139-5p demonstrated several-fold increases in DM rats and INS-1 cells (data not shown) and was reduced by liraglutide treatment. [score:3]
Liraglutide reduces miR-139-5p expression in pancreatic β-cells in vivo. [score:3]
Bcl-2 expression was significantly decreased in miR-139-5p transfected INS1 cell mo del (n = 3,*p<0.05). [score:3]
To address this question, we selected miR-139-5p, which is differentially expressed in the pancreatic tissue of liraglutide -treated rats compared with DM and control rats, based on gene-chip microarray analysis and confirmed by. [score:2]
0173576.g005 Fig 5 MiR-139-5p expression after liraglutide treatment by (*p<0.05). [score:2]
Considering the wide range of genes that are regulated by these miRNAs, we hypothesized that the anti-apoptotic effect of liraglutide on pancreatic β-cells is mediated through specific miRNAs (i. e. miR-139-5p). [score:2]
MiR-139-5p expression in INS-1 cells treated with palmitic acid (PA) and palmitic acid+ liraglutide (PA+Liar) (n = 3,*p<0.05). [score:2]
The other is that MicroRNA-139-5p suppresses 3T3-L1 preadipocyte differentiation through Notch and IRS1/PI3K/Akt insulin signaling pathways[29]. [score:2]
MiR-139-5p expression after liraglutide treatment by qRT-PCR (*p<0.05). [score:2]
First, we identified miR-139-5p as a novel miRNA that is regulated by palmitic acid and liraglutide. [score:2]
Bcl-2 expression was significantly decreased in the miR-139-5p mimics group compared with the Mock group (Mock group 1.0 vs mimics group 0.44, P<0.05). [score:2]
Whether miR-139-5p directly targets Bcl-2 within the Bcl-2 3′-UTR in the luciferase reporter analysis need to be further investigated. [score:2]
MiR-139-5p has been reported to promoting apoptosis by targeting c-Met and BCL2 in cancer cells [12, 23]. [score:2]
Cells were cotransfected with the luciferase reporter vector containing wild-type (IRS1-WT) or mutated (IRS1-Mut) 3’-UTR of IRS1 and miR-139-5p mimic (miR-139-5p) or control oligonucleotides (NC). [score:1]
These data suggest that miR-139-5p may mediate the anti-apoptotic effect of liraglutide in pancreatic tissue. [score:1]
Cells were divided into control, PA and PA+Lira group, which respectively treated with vehicle, palmitic acid (0.5nmol/L) or palmitic acid (0.5mmol/L) + liraglutide (100nmol/L) for 48 h. Cells were treated with negative control (B) or miR-139-5p mimics (C), incubated with annexin V and PI, and analyzed by confocal microscope. [score:1]
The relative mRNA levels of miR-139-5p in mock group, NC group and mimics group were 1.0, 0.93 ± 0.15, and 0.23 ± 0.06. [score:1]
MiR-139-5p mediated suppression of hRluc/hluc activity was calculated as the ratio of hRluc/hluc in miR-139-5p -transfected cells to hRluc/hluc in control oligotransfected cells. [score:1]
0173576.g009 Fig 9 Cells were treated with Mock, NC (negative control) and miR-139-5p Mimics for 24h. [score:1]
There were seven miRNAs reduced by over 50% (miR-380-5p, miR-139-5p, miR-743b-5p, miR-212-3p, miR-132-5p, miR-3592, and miR-201-5p) after liraglutide treatment. [score:1]
miR-139-5p mimics group: 2.7±0.3) (Fig 8D). [score:1]
Induction of miR-139-5p was observed in diabetic rats and INS-1 cells treated with liraglutide. [score:1]
0173576.g012 Fig 12 Effect of transfection with miR-139-5p mimics on IRS1 expression level in INS-1 cells measured by (A) and Western Blot (B and C) (n = 3,#p<0.05). [score:1]
0173576.g008 Fig 8 Cells were treated with negative control (B) or miR-139-5p mimics (C), incubated with annexin V and PI, and analyzed by confocal microscope. [score:1]
It was 0.52 ± 0.04 and 1.00 ± 0.06 for the rno-miR-139-5p group with wild-type carriers and the negative control group with mutant carriers, respectively. [score:1]
S1 Fig Cells were treated with Mock, NC (negative control) and miR-139-5p Mimics for 24h. [score:1]
0173576.g011 Fig 11 Cells were cotransfected with the luciferase reporter vector containing wild-type (IRS1-WT) or mutated (IRS1-Mut) 3’-UTR of IRS1 and miR-139-5p mimic (miR-139-5p) or control oligonucleotides (NC). [score:1]
We analysis the level of Bcl-2 in miR-139-5p transfected INS1 cell mo del (Fig 9). [score:1]
After overnight incubation, cells were transfected with 50 nM of rno-miR-139-5p -mimics or their respective negative controls (RiboBio, Guangzhou, China) using Lipofectamine [TM]RNAMiX (Invitrogen) according to the manufacturer’s instructions. [score:1]
Descriptions of the binding site of rno-miR-139-5p and the IRS1 gene are presented on the miRDB website. [score:1]
The constructs were cotransfected with miR-139-5p or a negative control (miR-139-5p-NC) into 293T cells using Lipofectamine 2000 (Invitrogen, USA). [score:1]
Whether inhibition of IRS1 can promote the effects of miR-139-5p on apoptosis of INS-1 cells needs to be further investigated. [score:1]
Regarding the rno-miR-139-5p group with mutant carriers, the relative activity was 0.92 ± 0.06 (Fig 11). [score:1]
Cells were treated with Mock, NC (negative control) and miR-139-5p Mimics for 24h. [score:1]
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4
[+] score: 150
The screening standard required that the miRNA appear in all databases and have a 2 to 10-fold upregulation in expression, although multiple genes are predicted by several algorithms (TargetScan, miRanda and PicTar) as potential miR-139-5p targets. [score:10]
As the upregulation of Lis1 can promote the occurrence of certain developmental events in the rat brain, miR-139-5p modulates rat brain development thorugh the regulation of Lis1 expression. [score:9]
Multiple algorithms (TargetScan, miRanda and PicTar) for predicting the putative targets of miR-139-5p identified several potential targets, such as Lis1, Capn8, Gmfb, Mapk1, Dclk1, Vim, Mgst1, Gnb1, Klf15 and Cdkn1b. [score:7]
These results indicate a downregulation in miR-139-5p expression during rat brain development. [score:7]
Due to the significant change in miR-139-5p expression during rat brain development, our data suggest that Lis1 is a target for miR-139-5p. [score:6]
As Lis1 is associated with neuronal migration, we speculate that miR-139-5p regulates rat cortical neuronal migration by modulating the expression of certain target genes. [score:6]
miR-139-5p may also contribute to rat brain development by affecting the expression of several other putative targets (30, 42, 43). [score:6]
Furthermore, we confirmed that miR-139-5p targets Lis1 and inhibits its expression, as confirmed by luciferase assay. [score:6]
The microarray results revealed that the expression of miR-139-5p was decreased in the brains of Sprague-Dawley rats (on days 20–80), and that Lis1 is a target of miR-139-5p. [score:5]
We cloned 400 bp of the Lis1 3′ untranslated region (3′UTR) containing the 7-bp target site for miR-139-5p into the SpeI/ HindIII sites of a luciferase gene in the pMIR-REPORT luciferase vector (Ambion, Shanghai, China). [score:5]
There was an inhibitory effect of miR-139-5p on the expression of Lis1 in the PC12 cells transfected with pre-miR-139-5p after 24 h (Fig. 3B). [score:5]
The luciferase activity of the wild-type plasmid was suppressed by approximately 42% at 24 h in the PC12 cells transfected with miR-139-5p mimics, while the activity of the mutant plasmid was not suppressed (Fig. 2B). [score:5]
The data presented in our study suggest an important role of miR-139-5p in regulating cell migration, thus offering a novel target for the development of therapeutic agents against focal cortical dysplasia. [score:5]
Transfection with miR-139-5p inhibited the protein expression of Lis1 by approximately 60 and 90% by using 100 and 300 pmol pre-miR-139-5p, respectively (Fig. 3D). [score:5]
It can be concluded that the upregulation of Lis1 in the rat brain is at least partially caused by a reduction in miR-139-5p. [score:4]
miR-139-5p modulates rat brain development by targeting Lis1. [score:4]
Wild-type or mutant Lis1 3′UTR was constructed in the luciferase reporter plasmid for conducting luciferase targeting assays (Fig. 2B) as it contains the 7-bp target site for miR-139-5p and the mutant 7-bp site. [score:4]
Sixty days after the rat mo dels were established, miR-139-5p was administered, and this led to the marked downregulation of Lis1 mRNA (Fig. 5D) and protein levels (Fig. 5C). [score:4]
By contrast, there was a promotional effect of anti-miR-139-5p on the expression of Lis1 in the PC12 cells transfected with anti-miR-139-5p (Fig. 3C). [score:3]
At the same time, miR-139-5p was administered to the rats with focal cortical dysplasia; miR-139-5p administration markedly decreased the expression of Lis1. [score:3]
The prediction of miR-139-5p targets was performed using the following algorithms: PicTar (http://pictar. [score:3]
Analysis of miR-139-5p predicted targets. [score:3]
Among the miRNAs found with significant changes in expression, we selected miR-139-5p to clarify its function in the brain. [score:3]
The PC12 cells (5×10 [4]) were co -transfected with 150 ng of pMIR-REPORT, Lis1-3′UTR plasmid and 25 nM of either a stably-enhanced non -targeting small RNA oligonucleotide as a negative control (control), or miR-139-5p mimics (both from GenePharma Co. [score:3]
Furthermore, miR-139-5p expression was decreased in Sprague-Dawley rats (on days 20–80) with focal cortical dysplasia induced by liquid nitrogen lesions. [score:3]
miR-139-5p inhibits cell migration. [score:3]
Bioinformatic analysis for the target site of miR-139-5p in the Lis1 3′UTR revealed that mature miR-139-5p shares the same sequence in rats, mice and humans (Fig. 2A). [score:3]
Correlation between the expression of miR-139-5p and Lis1 in PC12 cells. [score:3]
As expected, we found that miR-139-5p plays a role in rat brain development. [score:2]
We identified and characterized miR-139-5p, indicating that the loss of miR-139-5p regulates cortical neuronal migration through the modulation of Lis1 expression. [score:2]
Cell migration assays revealed that miR-139-5p significantly inhibited the migration of PC12 and HCN-2 cells treated with or without Lis1 protein. [score:2]
Transwell assays revealed that miR-139-5p significantly inhibited the migration of PC12 and HCN-2 cells treated with Lis1 protein (Fig. 4A). [score:2]
miR-139-5p targets Lis1 mRNA as shown by luciferase assay. [score:2]
We confirmed that miR-139-5p was successfully transfected into the PC12 cells (Fig. 3A). [score:1]
In the miR-139-5p administration group, miR-139-5p was injected into the rat brains using a rat brain locator at a 5 mg/kg dose on days 40 and 50, and brain tissue was obtained on day 60. [score:1]
Twenty Sprague-Dawley rats with cortical dysplasia were randomly divided into two groups: the mo del group and the miR-139-5p administration group. [score:1]
, Shanghai, China) as a negative control (control), or miR-139-5p mimics (stably enhanced miR-139-5p oligonucleotide; GenePharma Co. [score:1]
Additionally, it was found that miR-139-5p altered cell morphology in the rat brain, as indicated by (Fig. 6). [score:1]
The migration ability of the PC12 and HCN-2 cells was enhanced only upon the addition of Lis1 protein; this enhanced migration was attenuated by transfection with miR-139-5p. [score:1]
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of miR-139-5p. [score:1]
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5
[+] score: 149
As shown in Fig.   2B, Ucn-1 upregulated significantly the expression of miR-125a-3p and miR-324-3p, meanwhile it downregulated the expression of miR-139-3p. [score:11]
Figure  2 confirms that the addition of Ucn-1 in reperfusion significantly upregulated the expression of miR-125-3p and miR-324-3p, meanwhile it downregulated miR-139-3p. [score:9]
In this way, Ucn-1 induced miR-139-3p inhibition under I/R might be beneficial, as it will avoid the associated detrimental effects of PDE4 inhibition, although the effect of Ucn-1 on the expression of PDE4 needs further confirmation. [score:7]
Ucn-1 affords acute cardioprotective effects, but also modulates the expression of miR-125a-3p, miR-324-3p, and miR-139-3p, whose overexpression alters the expression of different genes. [score:7]
Remarkably, the upregulation of miR-125a-3p and miR-324 expression by Ucn-1 involved ERK1/2 activation; whereas, Epac2 was implicated in miR-139-3p and miR-324 regulation. [score:7]
We observed that Ucn-1 differentially regulates the expression of miR-125a-3p, miR-324-3p and miR-139-3p whose overexpression modulates several genes associated with a wide range of heart functions as cell stress, metabolism, cell survival and apoptosis. [score:6]
Furthermore, Epac2 specific inhibition with ESI-05 (10 μM) [16], blocked the effect of Ucn-1 on miR-324-3p (Fig.   4B) and miR-139-3p (Fig.   4C) regulation, but not miR-125a-3p expression (Fig.   4A). [score:6]
In contrast, the expression of miR-139-3p was enhanced under I/R, but following the administration of Ucn-2 miR-139-3p was efficiently downregulated as illustrated in Fig.   5F. [score:6]
Ucn-1 enhanced significantly the expression of both miR-125a-3p (Fig.   4A) and miR-324-3p (Fig.   4B), meanwhile Ucn-1 downregulated miR-139-3p (Fig.   4C), confirming the data obtained in perfused hearts (Fig.   2B). [score:6]
Interestingly, cells pretreatment with PD 098059 prevented Ucn-1 upregulation of miR-125a-3p (Fig.   4A) and miR-324-3p (Fig.   4B), but it did not affect miR-139-3p (Fig.   4C) expression levels during cells reperfusion. [score:6]
Ucn-1 inverted the effect of I/R and enhanced the expression of miR-125a-3p and miR-324-3p, meanwhile it decreased miR-139-3p expression. [score:5]
miR-139-3p, but not Ucn-1, also inhibited the expression of PDE4a, a critical protein involved in cAMP hydrolysis and heart contraction [44]. [score:5]
We found that, after I/R, the expression of miR-125a-3p (Fig.   4A) and miR-324-3p (Fig.   4B) decreased, whereas the expression of miR-139-3p increased (Fig.   4C). [score:5]
In addition, we found that the incubation of cardiac myocytes with 8CPT (10 μM), specific agonist of Epac1 and 2 [16], mimicked mostly the effect of Ucn-1. The administration of 8CPT prevented I/R -induced changes on the expression of miR-324-3p and miR-139-3p; meanwhile it did not affect the change induced by I/R of miR-125a-3p expression. [score:5]
Altogether, these data confirm in I/R animal mo del that infusion of Ucn-2 right before reperfusion regulates the expression of, at least, significantly miR-324-3p and miR-139-3p. [score:4]
Figure 3Urocortin-1 regulates miR-125a-3p, miR-324-3p and miR-139-3p expression in isolated cardiac myocytes. [score:4]
An other recent study demonstrated that miR-139-5p is downregulated in left ventricular tissue isolated from patients undergoing remote conditioning [31]. [score:4]
These data reveal that Ucn-1, through miR-125a-3p, miR-324-3p and miR-139-3p, might target multiple genes involved in different signaling pathway implicated in cardioprotection, which will induce synergetic beneficial effects. [score:3]
Similarly, Ucn-2 infusion in the animal mo del of I/R modulated the expression of miR-324-3p and miR-139-3p, but it failed to recover completely miR-125a-3p levels. [score:3]
Herein, we demonstrated that Ucn-1 decreased miR-139-3p’s levels and increased the expression of FoxO1 under I/R, which consequently will be beneficial for cardiac myocytes survival. [score:3]
To validate microarray results, we further examined the expression of miRNAs using qRT-PCR in samples from Langendorff-perfused hearts undergoing the same protocol as in Fig.   1. We focused on 6 miRNAs, miR-30c-2, miR-29a-3p, miR-125a-3p, miR-139-3p, miR-320, and miR-324-3p, which role in cardioprotection is still unknown. [score:3]
To ensure miRNAs mimics cells delivery, Lentivirus -expressing miR-125a-3p (LV-miR-125a-3p), Lentivirus-miR-139-3p (LV-miR-139-3p) and Lentivirus-miR-324-3p (LV-miR-324-3p) were constructed by cloning the pre-microRNA sequence in plasmid (pSIN-DUAL-GFP). [score:3]
Figure  3 shows that the expression of miR-125a-3p and miR-324 are increased significantly upon treatment with Ucn-1. In contrast, the level of miR-139-3p did not change significantly in cardiac myocytes incubated with any of the used Ucn-1 doses. [score:3]
Bar graphs showing fold changes in the expression of miR-125a-3p (A), miR-324-3p (B) and miR-139-3p (C) in isolated cardiac myocytes treated 10 minutes with increasing concentrations of Ucn-1 (2, 10 and 50 nM). [score:3]
On the other hand, we found that miR-139-3p overexpression reduced significantly the transcription factor FoxO1, which is essential for sustaining cardiac cells metabolism and viability [41]. [score:3]
Urocortin-1 modulates the expression of miR-125a-3p, miR-324-3p, and miR-139-3p in adult cardiac myocytes. [score:3]
In the current study, we demonstrated that the addition of Ucn-1 or Ucn-2 in the beginning of reperfusion changed the expression of miR-125a-3p, miR-324-3p, and miR-139-3p in different experimental mo dels of I/R. [score:3]
Similarly, Fig.   6B shows that cardiac myocyte transfection with LV-miR-139-3p significantly attenuated the expression of PDE4a and FoxO1. [score:3]
Therefore, Ucn-2 was used at 150 µg/Kg to examine the expression of miR-125a-3p, miR-324-3p, and miR-139-3p in hearts’ samples taken 24 hours after surgery. [score:3]
Nevertheless, changes in the levels of miR-29a-3p, miR-30c-2, and miR-320 were not significantly affected by Ucn-1. To assess the endogenous expression of miR-125a-3p, miR-324-3p, and miR-139-3p, we treated isolated cardiac myocytes with different concentrations of Ucn-1 (2, 10 and 50 nM). [score:3]
Moreover, Ucn-1 evoked changes in others genes regulated by miR-125a-3p, miR-324-3p and miR-139-3p were not significantly different (data not shown). [score:2]
Altogether, these data suggest that Ucn-1 applied on the onset of reperfusion regulates differentially miR-125a-3p, miR-324-3p and miR-139-3p through ERK1/2 and/or Epac2 signaling pathways. [score:2]
Therefore, we examined the implication of ERK1/2 and Epac2 signaling pathway in Ucn-1 regulation of miR-125a-3p, miR-324-3p and miR-139-3p. [score:2]
The role of miR-125a-3p, miR-324-3p, and miR-139-3p in cardioprotection is still unclear. [score:1]
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6
[+] score: 44
Among the nine T-cell miRNAs affected by TNF-α and downregulated in RA T cells, the expression levels of miR-139-3p, miR-204, miR-214, and miR-760 were increased in patients using biologic agents. [score:6]
Each scatter spot representing average normalized expression level of miRNA in three repeats of each treatment; (b) 13 miRNAs exhibiting aberrant expression in Jurkat cells cultured with TNF-α (20 ng/mL) for 7 days; (c) decreased expression of miR-139-3p, miR-204, miR-760, miR-524-5p, miR-136, miR-548d-3p, miR-214, miR-383, and miR-887 in RA T cells miRNA, compared with normal T cells. [score:6]
The expression levels of 12 miRNAs, including miR-139-3p, miR-204, miR-760, miR-432, miR-524-5p, miR-136, miR-548d-3p, miR-206, miR-214, miR-383, miR-224, and miR-887 were significantly lower, whereas the expression level of miR-146a was significantly higher, in Jurkat cells after being cultured with TNF-α for 7 days (fold change > 4, p < 0.05, Fig.   1b). [score:5]
Initially, our studies showed that among the expression of T cell miRNAs affected by TNF-α in Jurkat cells, the expression levels of miR-139-3p, miR-204, miR-760, miR-383, miR-524-5p, miR-136, miR-548d-3p, and miR-214 were significantly decreased in RA T cells. [score:5]
The expression levels of miR-139-3p, miR-204, miR-214, and miR-760 increased in RA patients using biologic agents. [score:3]
After adjusting for age and sex using multiple linear regression analysis (Table  2), RA patients with RF positivity had a significant 0.33-fold decrease (p = 0.039; 95% confidence interval [CI] 0.12–0.94) and the use of biologic agents had a significant 2.84-fold increase (p = 0.039; 95% CI 1.06–7.64) in miR-139-3p expression levels. [score:3]
Expression levels of miR-139-3p, miR-204, miR-214, and miR-760 were correlated with the use of biologic agents. [score:3]
The expression levels of miR-139-3p, miR-204, miR-214, and miR-760 increased in RA patients receiving biologic agents. [score:3]
With simple linear regression analysis, expression levels of miR-139-3p showed a significant correlation with rheumatoid factor (RF) positivity and the use of biologic agents. [score:3]
Decreased expression of miR-139-3p, miR-204, miR-760, miR-524-5p, miR-136, miR-548d-3p, miR-214, miR-383, and miR-887 were noted in RA T cells. [score:3]
The expression of miR-139-3p, miR-204, miR-760, miR-524-5p, miR-136, miR-548d-3p, miR-214, miR-383, and miR-887 was found to be significantly lower in RA T cells (p < 0.05), compared with controls (Fig.   1c). [score:2]
The fold changes of expression levels for these miRNAs were 0.42-fold for miR-139-3p, 0.43-fold for miR-204, 0.13-fold for miR-760, 0.32-fold for miR-524-5p, 0.45-fold for miR-136, 0.19-fold for miR-548d-3p, 0.37-fold for miR-214;0.36-fold for miR-383, and 0.14-fold for miR-887, compared with controls. [score:2]
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7
[+] score: 18
Other miRNAs from this paper: mmu-mir-30a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-132, mmu-mir-134, mmu-mir-135a-1, mmu-mir-138-2, mmu-mir-142a, mmu-mir-150, mmu-mir-154, mmu-mir-182, mmu-mir-183, mmu-mir-24-1, mmu-mir-194-1, mmu-mir-200b, mmu-mir-122, mmu-mir-296, mmu-mir-21a, mmu-mir-27a, mmu-mir-92a-2, mmu-mir-96, rno-mir-322-1, mmu-mir-322, rno-mir-330, mmu-mir-330, rno-mir-339, mmu-mir-339, rno-mir-342, mmu-mir-342, rno-mir-135b, mmu-mir-135b, mmu-mir-19a, mmu-mir-100, mmu-mir-139, mmu-mir-212, mmu-mir-181a-1, mmu-mir-214, mmu-mir-224, mmu-mir-135a-2, mmu-mir-92a-1, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-125b-1, mmu-mir-194-2, mmu-mir-377, mmu-mir-383, mmu-mir-181b-2, rno-mir-19a, rno-mir-21, rno-mir-24-1, rno-mir-27a, rno-mir-30a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-96, rno-mir-100, rno-mir-101a, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-132, rno-mir-134, rno-mir-135a, rno-mir-138-2, rno-mir-138-1, rno-mir-142, rno-mir-150, rno-mir-154, rno-mir-181b-1, rno-mir-181b-2, rno-mir-183, rno-mir-194-1, rno-mir-194-2, rno-mir-200b, rno-mir-212, rno-mir-181a-1, rno-mir-214, rno-mir-296, mmu-mir-376b, mmu-mir-370, mmu-mir-433, rno-mir-433, mmu-mir-466a, rno-mir-383, rno-mir-224, mmu-mir-483, rno-mir-483, rno-mir-370, rno-mir-377, mmu-mir-542, rno-mir-542-1, mmu-mir-494, mmu-mir-20b, mmu-mir-503, rno-mir-494, rno-mir-376b, rno-mir-20b, rno-mir-503-1, mmu-mir-1224, mmu-mir-551b, mmu-mir-672, mmu-mir-455, mmu-mir-490, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-504, mmu-mir-466d, mmu-mir-872, mmu-mir-877, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-872, rno-mir-877, rno-mir-182, rno-mir-455, rno-mir-672, mmu-mir-466l, mmu-mir-466i, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, rno-mir-551b, rno-mir-490, rno-mir-1224, rno-mir-504, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-466b-8, rno-mir-466d, mmu-mir-466q, mmu-mir-21b, mmu-mir-21c, mmu-mir-142b, mmu-mir-466c-3, rno-mir-322-2, rno-mir-503-2, rno-mir-466b-3, rno-mir-466b-4, rno-mir-542-2, rno-mir-542-3
The expression levels of miR-183 (4.61-fold), miR-96 (4.56-fold), and miR-182 (4.29-fold) were most highly up-regulated, whereas miR-122 (9.79-fold), miR-503 (5.88-fold), and miR-139-3p (1.94-fold) showed the greatest down-regulation as a result of 17α-E2 treatment. [score:9]
The expression levels of miR-183, miR-96, and miR-182 were most highly up-regulated, whereas miR-122, miR-503, and miR-139-3p exhibited the greatest down-regulation as a result of 17α-E2 treatment. [score:9]
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8
[+] score: 15
Eleven of the altered miRNAs were downregulated (miR-122, miR-93*, miR-872, miR-7*, miR-146a, miR-342-3p, miR-150, miR-139, miR-30a, miR-30e, miR-320), whereas three miRNAs, namely miR-463*, miR-34c* and miR-1188, were upregulated in the RYGB group. [score:7]
In particular, miR-342-3p, miR-320, miR-139-5p and miR-146a were predicted to be involved in multiple neurological transmitter and receptor-related pathways, as well as two major neurodegenerative disease -associated pathways (Parkinson's and Huntingtons diseases), suggesting that RYGB surgery may modulate neurological activity through a miRNA -mediated gut-brain axis. [score:5]
Decreased plasma levels of miR-342-3p, miR-320, miR-139-5p and miR-146a observed in our study suggest RYGB surgery impact on multiple neurodegenerative disease-related pathways. [score:3]
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9
[+] score: 13
Five differentially expressed microRNAs were randomly selected for validation, including three arterial highly expressed microRNAs (rno-miR-139-3p, rno-miR-423-5p, rno-miR-125b-5p) and two venous highly expressed microRNAs (rno-miR-1-3p, rno-miR-340-3p). [score:7]
For example, rno-miR-139-3p was consistently up-regulated in arterial plasma compared with venous plasma, though the absolute expression level might vary between individuals (Table 1). [score:5]
For example, seven microRNAs, including miR-1, miR-200c, miR-340, miR-342, miR-325, miR-139 and miR-500 contributed to the association with heart failure (P-value = 2.74e-3). [score:1]
[1 to 20 of 3 sentences]
10
[+] score: 13
Other miRNAs from this paper: hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-30a, hsa-mir-32, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-107, hsa-mir-129-1, hsa-mir-30c-2, hsa-mir-139, hsa-mir-181c, hsa-mir-204, hsa-mir-212, hsa-mir-181a-1, hsa-mir-222, hsa-mir-15b, hsa-mir-23b, hsa-mir-132, hsa-mir-138-2, hsa-mir-140, hsa-mir-142, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-154, hsa-mir-186, rno-mir-324, rno-mir-140, rno-mir-129-2, rno-mir-20a, rno-mir-7a-1, rno-mir-101b, hsa-mir-29c, hsa-mir-296, hsa-mir-30e, hsa-mir-374a, hsa-mir-380, hsa-mir-381, hsa-mir-324, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-15b, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19b-2, rno-mir-19a, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-24-1, rno-mir-24-2, rno-mir-27a, rno-mir-29c-1, rno-mir-30e, rno-mir-30a, rno-mir-30c-2, rno-mir-32, rno-mir-92a-1, rno-mir-92a-2, rno-mir-93, rno-mir-107, rno-mir-129-1, rno-mir-132, rno-mir-138-2, rno-mir-138-1, rno-mir-142, rno-mir-146a, rno-mir-154, rno-mir-181c, rno-mir-186, rno-mir-204, rno-mir-212, rno-mir-181a-1, rno-mir-222, rno-mir-296, rno-mir-300, hsa-mir-20b, hsa-mir-431, rno-mir-431, hsa-mir-433, rno-mir-433, hsa-mir-410, hsa-mir-494, hsa-mir-181d, hsa-mir-500a, hsa-mir-505, rno-mir-494, rno-mir-381, rno-mir-409a, rno-mir-374, rno-mir-20b, hsa-mir-551b, hsa-mir-598, hsa-mir-652, hsa-mir-655, rno-mir-505, hsa-mir-300, hsa-mir-874, hsa-mir-374b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-874, rno-mir-17-2, rno-mir-181d, rno-mir-380, rno-mir-410, rno-mir-500, rno-mir-598-1, rno-mir-674, rno-mir-652, rno-mir-551b, hsa-mir-3065, rno-mir-344b-2, rno-mir-3564, rno-mir-3065, rno-mir-1188, rno-mir-3584-1, rno-mir-344b-1, hsa-mir-500b, hsa-mir-374c, rno-mir-29c-2, rno-mir-3584-2, rno-mir-598-2, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
Furthermore, we and Gorter et al. 24 observed the up-regulation of miR-17-5p, miR-20a-5p, miR-23a-3p and the down-regulation of miR-139-5p, whereas we and Bot et al. 23 observed the down-regulation of miR-551b-3p. [score:10]
Another subgroup of miRNAs displayed an opposite pattern, i. e. decreased expression during latency: miR-7a-1-3p, miR-107-3p, miR-138-5p, miR-139-3p, miR-186-5p, miR-204-5p, miR-222-3p, miR-324-3p and miR-505-3p were significantly decreased during latency (peak at 4 days after SE), then gradually returned to control levels (Fig. 2, Supplementary Fig. S2). [score:3]
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11
[+] score: 12
A recent evidence showed that the processing of pre-miR-139 is blocked by inhibitors induced by Hypoxic Ischemia (HI), resulting in the down-regulation of mature miR-139-5p and a consequent up-regulation of Human Growth and Transformation Dependent Protein (HGTD-P), a proapoptotic protein (Qu et al., 2014). [score:9]
MiR-139-5p inhibits HGTD-P and regulates neuronal apoptosis induced by hypoxia-ischemia in neonatal rats. [score:3]
[1 to 20 of 2 sentences]
12
[+] score: 11
Other miRNAs from this paper: rno-mir-103-2, rno-mir-103-1, rno-mir-132, rno-mir-214, rno-mir-487b
qRT-PCR analysis showed that the expression levels of miR-139-3p,-339-3p and -132-3p were up-regulated, and the expression levels of miR-487b, -2985 and -34b were down-regulated during bone loss (Fig. 2b). [score:11]
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13
[+] score: 9
analysis of the hypertrophy markers ANF and BNP in transfected NRVMs showed that miR-139–5p and miR-374 mimics markedly increased the expression of ANF and BNP, while miR-324–5p, miR-153, and miR-141 mimics did not significantly affect the expression (unpublished data). [score:5]
For example, it has been reported that Igf1r is a target of miR-1 [55], miR-139 [56], miR-378 [57], miR-99a [58], and miR-497 [59]. [score:3]
We attempted to verify the effects of these six miRNAs (miR-185, miR-139–5p, miR-374, miR-324–5p, miR-153, and miR-141) on myocardial hypertrophy. [score:1]
[1 to 20 of 3 sentences]
14
[+] score: 9
In addition to miR-124a, stroke downregulates miR-9 and miR-139 in neural progenitor cells and these miRNAs have been predicted to target Notch and Hes1 [34] (www. [score:6]
org), suggesting that miR-9 and miR-139 could also regulate the Notch signaling pathway after stroke. [score:2]
In addition, the neural progenitor cells isolated by LCM exhibited increases in miR-146a, miR-146b, miR-210, miR-19b and miR-378 and decreases in miR-128, miR-291a-3p, and miR-139-5p (Fig. 3A to 3C), which are consistent with the array data findings. [score:1]
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15
[+] score: 7
In contrast, 3 miRNAs (miR-499, miR-1, miR-133a, and miR-466b) were upregulated in the denervated muscle and 3 miRNAs (miR-329, miR-204, and miR-139-3p) were downregulated after 6 months. [score:7]
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16
[+] score: 5
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-18a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-106a, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-99a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-127, mmu-mir-145a, mmu-mir-146a, mmu-mir-129-1, mmu-mir-206, hsa-mir-129-1, hsa-mir-148a, mmu-mir-122, mmu-mir-143, hsa-mir-139, hsa-mir-221, hsa-mir-222, hsa-mir-223, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-122, hsa-mir-125b-1, hsa-mir-143, hsa-mir-145, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-146a, hsa-mir-206, mmu-mir-148a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-21a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-129-2, mmu-mir-103-1, mmu-mir-103-2, rno-let-7d, rno-mir-335, rno-mir-129-2, rno-mir-20a, mmu-mir-107, mmu-mir-17, mmu-mir-139, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-125b-1, hsa-mir-26a-2, hsa-mir-335, mmu-mir-335, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-17-1, rno-mir-18a, rno-mir-21, rno-mir-22, rno-mir-26a, rno-mir-99a, rno-mir-101a, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-126a, rno-mir-127, rno-mir-129-1, rno-mir-143, rno-mir-145, rno-mir-146a, rno-mir-206, rno-mir-221, rno-mir-222, rno-mir-223, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-486-1, hsa-mir-499a, mmu-mir-486a, mmu-mir-20b, rno-mir-20b, rno-mir-499, mmu-mir-499, mmu-mir-708, hsa-mir-708, rno-mir-17-2, rno-mir-708, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-486b, rno-mir-126b, hsa-mir-451b, hsa-mir-499b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-130c, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, hsa-mir-486-2, mmu-mir-129b, mmu-mir-126b, rno-let-7g, rno-mir-148a, rno-mir-196b-2, rno-mir-486
By 18 wks of E [2] treatment, the mammary glands were characterized by lobular involution and hyperplasia, and only 1 miRNA was down-regulated (miR-139) and 5 miRNAs were up-regulated (miR-20b, miR-21, miR-103, mir-107, miR-129-3p, and miR-148a). [score:5]
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17
[+] score: 5
For example, miR-106b, miR-21, miR- 22, miR-19b and miR-25 are known to regulate PTEN and miR-27 and miR-139 repress FoxO1 translation through direct binding to the 3′-UTR [31], [32], [33], [34], [35], [36], [37], [38]. [score:5]
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18
[+] score: 4
We found common expression of 9 miRNAs (miR-132, miR-137, miR-139, miR-29a, miR-324, miR-352, miR-282, miR-146a, and miR-23a) when our data were compared to a data set describing miRNA expression 60 d after pilocarpine -induced status epilepticus [24]. [score:4]
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19
[+] score: 3
Other female-biased miRNAs showing large differences in expression included miR-139-3p (5-fold), miR-501 (6-fold), and miR-421* (2.6-fold). [score:3]
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20
[+] score: 3
There were 8 miRNAs with fold changes in expression greater than 3 [miR-490-5p (FC = 9.44), miR-547-3p (FC = 4.77), miR-24-1-5p (FC = 3.78), miR-200a-5p (FC = 3.55), miR-139-3p (FC = 3.51), miR-139-5p (FC = 3.46), miR-676 (FC = 3.32), and miR-532-3p (FC = 3.07)]. [score:3]
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21
[+] score: 1
The authors also demonstrated that resilient rats differed from vulnerable rats in the set of multiple blood-circulating miRNAs, namely, reduction in miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p in resilient animals and reduction in miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p and miR-532-5p levels in vulnerable animals. [score:1]
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