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73 publications mentioning mmu-mir-135a-1

Open access articles that are associated with the species Mus musculus and mention the gene name mir-135a-1. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 253
Other miRNAs from this paper: mmu-mir-135a-2
Thus, the present data demonstrate that in addition to degradation of the translation of its target gene Siah1, miR-135a also regulates the level of other proteins indirectly by controlling the expression of ubiquitin-specific proteases. [score:9]
The action of miR-135a on Siah1a expression was not by inducing mRNA target degradation as miR-135a inhibitor had no effect on Siah1a mRNA expression in the 2 groups (Figure 3D). [score:9]
Three publicly accessible miRNA target prediction programs, Pictar, TargetScan 5.2 and miRanda predict that Siah1 is a target of miR-135a. [score:7]
It is not surprising that the antibody cannot completely nullify the effect of miR-135a inhibitor because miRNA regulates a number of target genes simultaneously and the treatment nullifies the effect of Siah1 only. [score:6]
Here, we provide evidence that miR-135a regulates the first cell division mediated by suppressing the expression of Siah1a, which in turns affect destabilization of chemokinesin DNA binding protein (Kid), which mediates chromosome compaction and is degraded by the proteasome pathway during mitosis [30], [31]. [score:6]
Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid). [score:6]
It was found that the Siah1a protein expression was increased in both groups (Figure 3C and D), confirming that miR-135a regulated the expression of Siah1a. [score:6]
For assessing Siah1a expression upon miR-135a knockdown, miR-135a inhibitor was microinjected into zygotes or transfected into HeLa cells. [score:6]
0027878.g002 Figure 2Microinjection of miR-135a inhibitor suppressed the development of 1-cell embryo. [score:6]
Mouse preimplantation embryos expressed developmental stage-specific miRNAs [4], [37], [38] and miR-135a is specifically expressed in the zygotic stage. [score:6]
Although Siah1a is essential for normal development, our study showed that the level of Siah1a needs to be tightly control at the zygotic stage, as excessive amount of the enzyme induced by miR-135a inhibitor inhibited first cleavage division. [score:6]
Microinjection of miR-135a inhibitor suppressed the development of 1-cell embryo. [score:6]
Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. [score:5]
The expression of Siah1a in miR-135a inhibitor -treated cells and zygotes was also examined. [score:5]
About 10 pL of 25 µM locked nucleic acid modified miR-135a inhibitor (miRCURY LNA™ microRNA inhibitors, Exiqon, Vedbaek, Denmark) was microinjected into the cytoplasm of the zygotes. [score:5]
Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. [score:5]
Here, we observed that the Kid level was decreased upon miR-135a inhibition; consistent with the reduction in Siah1a expression mediated by zygotic increase of miR-135a enhances the level of Kid in zygotes for normal first cleavage division. [score:5]
Microinjection and in vitro embryo cultureAbout 10 pL of 25 µM locked nucleic acid modified miR-135a inhibitor (miRCURY LNA™ microRNA inhibitors, Exiqon, Vedbaek, Denmark) was microinjected into the cytoplasm of the zygotes. [score:5]
MiR-135a inhibitor (human miR-135a is identical to mouse miR-135a and the same inhibitor can be used), or scramble control were transfected together with reporter constructs into HeLa cells (American Type Culture Collection, Manassas, VA). [score:5]
Western blotting and 3′UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. [score:5]
Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. [score:5]
Therefore, we examined the effect of miR-135a inhibitor on Kid expression. [score:5]
The inhibitory action of miR-135a knockdown on the first cell cleavage could result from perturbation of the proteolysis of Siah1a substrates. [score:4]
We found that miR-135a was expressed in all preimplantation embryos but the level was significantly higher at the zygote stage than at other stages of development (Figure 1B). [score:4]
MiR-135a inhibition suppresses first cell cleavage. [score:4]
The expressions of miR-135a at different developmental stages were assessed by qPCRs with (A) and without preamplification (B) on 5 embryos (n = 5). [score:4]
Our previous miRNA profiling of mouse spermatozoa, oocytes and preimplantation embryos indicated that miR-135a was highly expressed in zygotes, but decreased gradually with development (). [score:4]
Transfection of miR-135a inhibitor into HeLa cells suppressed the function of endogenous miR-135a, and thus significantly increased the activity of the luciferase reporter when compared to cells transfected with the scramble control (Figure 3B). [score:4]
0027878.g001 Figure 1The expressions of miR-135a at different developmental stages were assessed by qPCRs with (A) and without preamplification (B) on 5 embryos (n = 5). [score:4]
Third, the inhibitory activity of miR-135a knockdown at zygote stage was partially nullified by co-injection of anti-Siah1a antibody. [score:4]
Effects of miR-135a inhibition on the development of mouse preimplantation embryos. [score:4]
We next tested whether Siah1a mediated the inhibitory effect of miR-135a on embryo development. [score:4]
The action of miR-135a is, at least partially through down-regulation of Siah1a. [score:4]
Our previous miRNA profiling showed that miR-135a was highly expressed in the zygotes and decreased thereafter (Figure 1A). [score:3]
When the seed region of the reporter was mutated, miR-135a inhibitor did not affect the luciferase activity (Figure 3B). [score:3]
Siah1a specific antibody or water control was co -injected with miR-135a inhibitor or scramble control into pronucleated zygotes. [score:3]
Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. [score:3]
The expression levels of Siah1a did not increase after the 4-cell stage when the miR-135a level was low. [score:3]
The hypothesis was tested by microinjection of miR-135a inhibitor into the pronucleated zygotes at 21-hour post-human chorionic gonadotrophin (hCG) administration. [score:3]
MiR-135a knockdown significantly reduced cell division of zygotes when compared to those injected with scramble control; more than 30% of the miR-135a inhibitor -treated zygotes failed to advance to the 2-cell stage while more than 94% of the scramble control -injected zygotes developed to the 2-cell embryo (Figure 2). [score:3]
Expression of miR-135a in preimplantation embryos. [score:3]
In this study, the expression of Siah1a was high in oocytes, and decreased in the zygotic stage when the level of miR-135a was high. [score:3]
Immunostaining showed that the Kid level was decreased in miR-135a inhibitor treated embryos (Figure 6B). [score:3]
Since Siah1a is involved in proteasomal degradation, we examined the action of miR-135a in ubiquitation by using proteasomal inhibitor MG-132. [score:3]
Here, we demonstrated that miR-135a is important for the first cell cleavage; microinjection of miR-135a inhibitor reduced the percentage of zygotes undergone first cell division by about 30%. [score:3]
MiR-135a regulates the expression of Siah1. [score:3]
Only about 60% of zygotes injected with miR-135a inhibitor developed to the 2-cell stage. [score:3]
It is interesting to note that the increased expression of miR-135a in the zygotes correlates with a gradual decrease of Siah1a from this stage (Figure 1 and 4). [score:3]
Either miR-135a inhibitor or scramble control was co -transfected with the luciferase reporter gene system, which included a vector carrying the luciferase reporter gene anchoring a Siah1a miR-135a potential binding site. [score:3]
Coinjection with Siah1a antibody partially nullified the effect of miR-135a inhibitor and about 80% of these embryos developed to the 2-cell stage (Figure 5). [score:3]
Siah1a antibody partially nullified the effect of miR-135a inhibitor microinjection. [score:3]
Second, miR-135a knockdown induced an increase in Siah1 protein in mouse zygotes and HeLa cells. [score:2]
0027878.g006 Figure 6 (A) Enhanced accumulation of ubiquitination complex was observed in MG-132 treated miR-135a inhibitor injected zygotes when compared to control embryos. [score:2]
This stage-specific expression of miR-135a prompted us to investigate its functional roles in zygotic development. [score:2]
Siah1a mediates the effect of miR-135a on embryo development in mice. [score:2]
MiR-135a expression in preimplantation mouse embryos. [score:2]
MiR-135a inhibitor did not affect the reporter activity when the Siah1a 3′UTR carried a mutated seed binding region. [score:2]
MiR-135a affects proteasomal degradation and expression of Kid. [score:2]
PicTar [32] identified that miR-135a potentially bound to position 365–387 of the 3′UTR of Siah1a (Figure 3A). [score:1]
First, luciferase reporter assay showed that miR-135a acted on the 3′UTR of Siah1 directly but not on the mutated seed binding region. [score:1]
The importance of miR-135a in preventing death of oocyte/zygote remains to be determined. [score:1]
Statistical significant differences were found between the miR-135a -injected embryos (circle) and the scramble control -injected embryos (triangle) and the untreated control (square). [score:1]
We hypothesized that miR-135a affected first zygotic cleavage. [score:1]
In summary, we have demonstrated that miR-135a is involved in the first cell cleavage in zygotes. [score:1]
0027878.g003 Figure 3. (A) Potential miR-135a binding site on 3′UTR of Siah1a, seed binding region were labeled in bold (position 380–386). [score:1]
MiR-135a regulates proteasomal degradation. [score:1]
Several observations indicate that the action of miR-135a is partially mediated through Siah1a. [score:1]
Mature miR-135a can be detected in mouse epididymal spermatozoa at a level that is 2.2-fold higher than that of oocytes. [score:1]
This study aimed to confirm this observation and to study the function of miR-135a in the zygotes. [score:1]
MicroRNA-135a inhibition and luciferase reporter assay. [score:1]
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2
[+] score: 235
Taken together these data suggest that mir-135a inhibits Nr3c2 mRNA translation by binding to either one or two sites present in the Nr3c2 3’ UTR; indirect effects of miR-124 on the MR endogenous protein expression have been observed both in N2a cells and CGN. [score:8]
A mutant reporter lacking the seed matches for miR-124 is unaffected by miR-124 overexpression, as expected, and is more than 60% inhibited by miR-135a overexpression. [score:7]
Venn diagram of miR-135a target genes predicted by three independent algoritms, microT v 3.0, TargetScan 5.2, TargetScan 5.2. [score:7]
By northern blot analysis we studied miR-135a expression in different structures of the adult mouse brain and in post-natal neurons (Figure S2): various expression levels were found in the brain areas analyzed, including the amygdala, with a higher relative expression in the cerebellum, as already described [30]. [score:7]
Moreover, we found a strong reduction of the MR expression after the combined overexpression of plasmids encoding for miR-135a and miR-124 (MR expression 60% of vector control transfection). [score:7]
Using three independent target prediction algorithms, DIANA-microT v 3.0, TargetScan 5.2, and PicTar, we narrowed the number of bioinformatic target candidates for miR-135a to 38 genes (Figure S3). [score:7]
Either the firefly reporter construct or the endogenous protein are significantly downregulated by miR-135a overexpression. [score:6]
The ability of miR-135a to negatively regulate MR expressions was confirmed by overexpressing miR-135a from a different plasmid in which the miRNA transcription is driven by an H1-promoter (Figure S7A and B). [score:6]
Next, to better understand the possible role of mir-135a and miR-124 downregulation in the context of the stress response, we searched for predicted mRNA targets. [score:6]
Transfection of N2a cells with miR-135a expression constructs, resulting in an increased concentration of mature miRNAs (Figure S5), directed a significant reduction of MR protein expression (p135a, Figure 4A and B). [score:6]
Here we show that acute stress downregulates miR-135a and miR-124 expression in the amygdala. [score:6]
Figure S7 MR down-regulation upon H1 promoter -driven expression of miR-135a. [score:6]
The inhibition of luciferase expression is tightly dependent on the presence of a sequence in the Nr3c2 3’ UTR perfectly complementary to the miR-135a seed region. [score:5]
Among miR-135a predicted target genes we found as a top-score target Nr3c2, coding for the brain corticosteroid receptor MR. [score:5]
For endogenous protein expression analysis, N2a cells and CGN (6 DIV) were transfected in 6-well plates with 4 µg of miRNA expression vectors or 100 nM LNA (scramble, LNA anti miR-135a or LNA anti miR-124 (Exiqon), respectively). [score:5]
Conversely to miRNA overexpression, the inhibition of endogenous miR-135a and miR-124 in CGN by LNA modified oligonucleotide transfections led to a statistically significant increase in the levels of endogenous MR protein (Figure 4C and D). [score:5]
As presented in Figure 3B, we were able to demonstrate the predicted interactions between miR-135a and the 3’ UTR of Nr3c2 mRNA by means of approximately 50% of decrease in the expression of the Nr3c2 3’ UTR reporter upon miR-135a overexpression, comparing to the co-transfection of the reporter with the empty vector. [score:5]
miR-135a is brain-specific, its expression is induced upon neuronal differentiation, and it is poorly expressed in other adult tissue [10, 11, 27– 29]. [score:5]
This was shown by transfection experiments with mutant reporter constructs containing the Nr3c2 3’ UTR mutated at the level of miR-135a seed binding sites, whose expression was unaffected by miRNA overexpression. [score:5]
In the present study we focused on the stress -induced downregulation of the brain-specific miR-135a and miR-124, and their possible role in the context of stress response. [score:4]
Finally, we established miR-124 and miR-135a as regulators of the MR expression in mouse N2a cells and CGN. [score:4]
miR-135a and miR-124 regulate the expression of the endogenous MR protein. [score:4]
Acute stress induces miR-135a and miR-124 downregulation in the amygdala. [score:4]
Therefore, the observed MR protein increase, related to miR-135a and miR-124 down-regulation, might be instrumental for the MR functional activation in response to the stress -induced increase of CORT levels. [score:4]
miR-135a and miR-124 regulate Nr3c2 mRNA expression. [score:4]
It will be interesting to study whether miR-124 and miR-135a dysregulation is implicated in stress-related or major depressive disorders where a decreased expression of the amygdala MR was found [56]. [score:4]
In addition, knocking down endogenous miR-135a and miR-124 in CGN we were able to confirm the ability of both these miRNAs to affect the expression of the MR in a different cell system. [score:4]
Furthermore, as shown by mutant constructs, miR-135a activity on Nr3c2 3’ UTR is direct and it is indeed strictly dependent on the integrity of the two cognate target sequences. [score:4]
Demonstrating that miR-135a and miR-124 are able to affect the MR expression, we suggest their functional role in the initial stress reaction by the activation of the corticosteroid signaling. [score:3]
These plasmids allow us to obtain high levels of U1 promoter -driven miR-135a and miR-124 expression, as shown by northern blot analysis (Figure S5). [score:3]
Indeed, we found that the transfection in neuroblastoma cells of miR-135a, that has two binding sites on the Nr3c2 3’ UTR, induces a strong suppression of the MR. [score:3]
We demonstrated that the overexpression in N2a cells of miR-135a and miR-124 determines a reduction of MR protein levels. [score:3]
Prediction analysis of the miR-135a targets was done using three prediction algorithms, microT v 3.0 (diana. [score:3]
As shown in Figure 5A acute stress induced a three-fold increase in the amygdala MR protein levels, this negatively parallels stress -induced alterations in miR-124 and miR-135a expression. [score:3]
Figure S3 miR-135a target prediction. [score:3]
Figure S2 Expression of miR-135a in different brain structures. [score:3]
Interestingly, a previous study aimed to the identification of miRNAs involved in kidney water–salt balance and blood pressure regulation, indicated the human NR3C2 gene as a potential target of miR-135a and miR-124 by mean of luciferase assays [41]. [score:3]
To validate the functionality of these putative interactions, the complete mouse Nr3c2 3’ UTR was cloned dowstream of the firefly luciferase coding sequence (Nr3c2 3’ UTR) and this construct was transiently transfected into Hela cells along with miR-135a and miR-124 expression vectors (p135a and p124). [score:3]
No expression of miR-135a and miR-124 was found in N2a cells (Figure S5, see empty vector lanes). [score:3]
A significant miR-135a expression was found in primary neuronal cultures of cerebellar granule neurons. [score:3]
Positions of mir-135a and miR-124 target sequences in the mouse annotated Nr3c2 3’ UTR and details of miRNA/mRNA base pairing are indicated. [score:3]
These findings demonstrate that mir-135a and mir-124 are able to negatively affect the expression of the endogenous MR. [score:3]
miRNA expression vector p135a was obtained by amplifying 301-bp from mmu-miR-135a-1 genomic sequence, containing 111 nt upstream and 100 nt downstream the miRNA stem-loop sequence, according to the miRBase Database (http://www. [score:3]
Northern blot analysis of miR-135a expression in various mouse brain structures: Str, Striatum; Cb, Cerebellum; Ctx, Prefrontal cortex; OB, Olfactory bulb; Hippo, Hippocampus; Thal, Thalamus; Hypo, Hypotalamus; Amy, Amygdala; CGN, Cerebellar granule neurons in culture for 6 days (D6). [score:3]
Moreover, qRT-PCR analysis indicated an approximately 30% reduction of the expression levels of miR-135a, validating our previous array data (Figure 2B). [score:3]
Thus, we conclude that mir-135a and mir-124 expression levels are sensitive to stress, as indicated by qRT-PCR for miR-124, and by both microarray and qRT-PCR for miR-135a. [score:3]
These reporter experiments indicate a direct functional interaction between miR-135a and the Nr3c2 3’ UTR and a no direct functional interaction between miR-124 and the Nr3c2 3’ UTR. [score:3]
0073385.g004 Figure 4(A) N2a cells were transfected with miR-135a (p135a) and miR-124(p124) overexpressing vectors as indicated. [score:3]
However, not much is known about miR-135a expression in the different brain regions. [score:3]
Figure S5 U1 promoter -driven miR-135a and miR-124 overexpression in Hela and N2a cells. [score:3]
We show that after two hours of mouse restraint miR-135a and miR-124 are negatively regulated. [score:2]
Among miRNAs negatively regulated, only one miRNA shows a log [2]-ratio < 1, namely miR-135a. [score:2]
We validated the predicted interaction between miR-135a and the mouse Nr3c2 3’ UTR by a luciferase assay, demonstrating a miR-135a induced reduction of Nr3c2 reporter expression. [score:2]
Hence, we tested the validity of miR-135a and miR-124 binding sites, ascertained by reporter assays from our and others labs, by further experiments on mouse cells expressing the MR protein. [score:2]
Nr3c2 reporter is regulated by miR-135a. [score:2]
To generate Nr3c2 mutant constructs Nr3c2 m135a and Nr3c2 m124, mutations of seed binding sites for miR-135a (Nr3c2 m135a) or miR-124 (Nr3c2 m124) were introduced into the Nr3c2 3’ UTR using synthetic oligonucleotides, by generating partially complementary PCR fragments. [score:2]
As shown by quantitative analysis of western blots (Figure 4B), overexpression of mir-135a caused a 50% reduction of MR protein levels, compared to the transfection with the empty vector. [score:2]
Two binding sites for miR-135a are present upstream and dowstream in the mouse Nr3c2 3’ UTR (Figure 3A), highly conserved in 15 and 14 species, respectively (Figure S4). [score:1]
Thus, the same miRNA, in concert with other miRNAs like miR-135a, might be responsible for the fine-tuning of corticosteroid receptors in order to maintain the correct MR/GR balance, necessary for effective coping with stress [6]. [score:1]
Figure S4 Sequence conservation of the miR-135a and miR-124 binding sites within the Nr3c2 3’ UTR. [score:1]
In summary, we report that miR-135a and miR-124 are important components of the stress signaling response in the brain. [score:1]
Beneath miRNA sequences, nucleotides mutated at the level of miRNA binding sites in the mutant constructs Nr3c2 m135a (mutated at both miR-135a seed binding sites) and Nr3c2 m124 (mutated at both miR-124 seed binding sites), are indicated (nts in bold). [score:1]
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3
[+] score: 188
To find out if CEBPD expression has direct correlation with miR-135a expression, we investigated the expression of miR-135a in U373MG cells either by overexpression of CEBPD or knock down of CEBPD. [score:9]
We obtained a consistent result in which the overexpression of CEBPD results in increasing expression of miR-135a (Fig.   3a), while knock down of CEBPD results in reduce expression of miR-135a upon IL-1β stimulation (Fig.   3b). [score:8]
Whereas, a recent study showed that miR-135a targeted to beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in neuron cells and downregulated in CSF and serum of AppTg mice [48]. [score:6]
Moreover, we revealed that the CEBPD -upregulated miR-135a can target to THBS1-3′UTR and resulted in its mRNA and protein degradations. [score:6]
Interestingly, miR-135a, a putative THBS1 mRNA binding suppressor, was observed to be upregulated by CEBPD in the global profiling of miRNA. [score:6]
In addition to miR-135a, several CEBPD -downregulated miRNAs including miR-9, miR-19b, miR-29a/b-1, miR-16, and miR-107 were found to be repressed in neurodegenerative diseases [50, 51]. [score:6]
We found that expression of antisense of miR-135a (A-135a) in primary astrocytes (Fig.   4c) or miR-135a antagomir (AM135a) in U373MG cells (Fig.   4f) can lead to increase THBS1 expression. [score:5]
qRT-PCR and Western blot confirmed that miR-135a levels and the expression of HA-tagged CEBPD protein from stable U373MG cells with pMT-CEBPD expression vector, respectively. [score:5]
b Two positions of the Thbs1 3′-untranslated region are predicted to be targets of miR-135a. [score:5]
d Induced miR-135a expression repress the THBS1 expression. [score:5]
In stable U373MG cells with DOX-inducible miR-135a expression system, the expression of miR-135a and the level of THBS1 mRNAs and proteins were examined by qRT-PCR, RT-PCR, and Western blot, respectively. [score:5]
The results of neurons growing in the CM from astrocyte expressing CEBPD or miR-135a provided a novel mechanism to explain the reduced neuronal neurite length and survival commonly observed in AD or other neuroinflammatory diseases. [score:5]
Since miR-135a is located at intron 1 of GLYCTK- AS1- 001 gene, we first made sure that increase expression of CEBPD can indeed induce the expression of GLYCTK- AS1- 001 transcripts (Fig.   S2). [score:5]
Upregulation of miR-135a was detected in the cerebrospinal fluid (CSF) of AD patients and a microarray profile of the brain of AD mice [46, 47]. [score:4]
In addition to our recent discovery that miR-135a plays an angiogenic role [27], we further demonstrated that astrocytic miR-135a participates in inhibition of neuronal viability and spatial learning ability in AppTg mice. [score:3]
c miR-135a expression is unaltered in primary Cebpd − /− astrocytes. [score:3]
Consistently, we also found that there is reduction in the length of neurons when incubated with CM containing either U373MG cells overexpressing either CEBPD or miR-135a (Fig. S3a, S3b). [score:3]
a miR-135a attenuates the expression of Thbs1. [score:3]
Doxycycline (2 μg/mL) was used to induce miR-135a expression. [score:3]
e IL-1β and CEBPD suppresses THBS1 transcription via miR-135a binding motif. [score:3]
Induced miR135a in primary astrocytes with DOX-inducible miR-135a expression system; qRT-PCR and western blot analysis confirmed that miR-135a, Thbs1 mRNAs, and proteins levels, respectively. [score:3]
Similar results were also obtained from co-transfecting various THBS1 3′UTR reporters with CEBPD, pre-miR-135a expression vectors, or IL-1β stimulation (Fig.   4d). [score:3]
Conditioned medium (CM) from stable U373MG cells with zinc-inducible CEBPD (a) or with DOX-inducible miR-135a (b) expression system were subjected to exam THBS1 by Western blot and added to primary neurons for 48 h. c Attenuated miR-135a in U373MG cells restore the neuronal nurite outgrowth. [score:3]
Next, we investigated whether inhibition of miR-135a can lead to the opposite effect of increasing THBS1 expression. [score:3]
a miR-135a expression increase in the brain tissues of AppTg mice. [score:3]
b CEBPD participate in IL-1β -induced miR-135a expression. [score:3]
Our results suggested that astrocytic CEBPD activation results in the impairment of spatial learning ability through activating miR-135a to suppress neurotropic factor THBS1. [score:3]
To confirm that Thbs1 3′UTR is indeed targeted by miR-135a, we constructed luciferase reporter plasmids that contained native or mutated seed sequences of Thbs1 3′UTR. [score:3]
Ko CY Chu YY Narumiya S Chi JY Furuyashiki T Aoki T Wang SM Chang WC The CCAAT/enhancer -binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2 -induced angiogenesis in Alzheimer's diseaseNeurobiol Aging 2014 28. [score:3]
It was observed that the expression of miR-135a still increased upon IL-1β treatment in primary Cebpd [+/+] but not in Cebpd [−/−] astrocytes (Fig.   3c). [score:3]
a CEBPD induces miR-135a expression. [score:3]
Enhanced expression of miR-135a was found in the brain of a 12-month-old AppTg mice but not in AppTg/Cebpd − /− mice (Figs.   6a and S4). [score:3]
miR-135a Neuronal viability Spatial learning ability Neuroinflammation Neuroprotective factor Neuroinflammation is a prominent feature of Alzheimer’s disease (AD) and has been suggested to play a role in AD progression [1– 3]. [score:3]
There is also no change in the length of primary neurons upon incubation with CM containing either astrocytes (Fig.   5b) or U373MG cells (Fig.   S3c) expressing antisense of miR-135a (A-135a). [score:3]
Liu CG Wang JL Li L Xue LX Zhang YQ Wang PC MicroRNA-135a and -200b, potential biomarkers for Alzheimer’s disease, regulate beta secretase and amyloid precursor proteinBrain Res 2014 49. [score:3]
In both studies, we found that increase expression of miR-135a attenuates the level of THBS1. [score:3]
Next, we wished to find out how CEBPD can increase the expression of miR-135a. [score:3]
miR-135a Can Target to THBS1 (Human)/Thbs1 (Mouse) 3′UTR and Contributes to the Repression of THBS1/ Thbs1. [score:3]
Subsequently, we explored whether CEBPD still regulate miR-135a in primary astrocytes. [score:2]
Fig. 5Astrocytic CEBPD and miR-135a regulate the extension of primary cortical neurons. [score:2]
We found that miR-135a repressed the native Thbs1 3′UTR reporter activities, but these effects were lost in construct with individual mutations of miR-135a binding motifs (Fig.   4b). [score:2]
miR-135a is a novel CEBPD responsive gene and first identified to regulate THBS1 transcription. [score:2]
The reporter assay were conducted by co-transfecting various mouse Thbs1 3′UTR reporters with miR-135a expression vector. [score:2]
The inconsistent results indicated that the regulation of miR-135a could be in a cell-type specific manner or because the variations of specimens of AD patients and age of the AppTg mice. [score:2]
Conditioned medium from primary Cebpd [+/+] or Cebpd − /− astrocytes with or without IL-1β treatment were subjected to exam Thbs1 by Western blot and added to primary neurons for 48 h. b Attenuated miR-135a in astrocytes restore the neuronal neurite outgrowth. [score:1]
The 3′-UTRs of THBS1 and Thbs1 genes and 5′-flanking region of GLYCTK-AS1-001 gene (host gene of intronic miR-135a) were cloned from U373MG cells by using the DNeasy Tissue Kit (QIAGEN, Düsseldorf, Germany) and PCR. [score:1]
The sections were incubated in pre-hybridization solution at 50 °C for 3 h and then in hybridization solution with digoxigenin-labeled, locked nucleic acid -modified miR-135a probe at 50 °C for 16 h. The sections were incubated in the phosphate-buffered saline diluted anti-digoxigenin-AP antibody (1:100) at room temperature for 1 h, washed with 2× standard saline citrate (SSC), 1.5× SSC, 0.2× SSC, incubated in blocking solution for 1 h at room temperature, washed with phosphate-buffered saline three times, then washed with 1× alkaline phosphatase buffer twice. [score:1]
Importantly, the miR-135a antagonist (AM135a) can effectively recuse the spatial learning ability of AppTg mice. [score:1]
Non-radioactive in situ hybridization was performed on 10 μm sections from mouse brain tissue blocks using the digoxigenin-labeled locked nucleic acid -modified detection probe (20 μM; 5′-TCACATAGGAATAAAAAGCCATA-3′; Exiqon, Tustin, CA) complementary to mature miR-135a and IsHyb in situ hybridization kit (BioChain, Hayward, CA) following the protocol from Exiqon. [score:1]
However, miR-135a is a glia-enriched miRNA and low in normal neuron cells [49]. [score:1]
CEBPD Activates miR-135a Transcription. [score:1]
miR-135a level in wild-type, AppTg, and AppTg/Cebpd − /− mice was analyzed by qRT-PCR (n = 2 per genotype). [score:1]
Our recent study demonstrated that prostaglandin 2 (PGE2) could repress THBS1 3′UTR reporter activity through a miR-135a binding motif. [score:1]
miR-135a signal was detected by in situ hybridization in the hippocampus and cortex of WT, AppTg, and AppTg/Cebpd − /− mice. [score:1]
We also found that the activation of miR-135a transcription was responsive to transcription factor CEBPD and represses THBS1 abundance in astrocytes. [score:1]
Intracerebral Injection of miR-135a Neutralizing Antagomir Decreases Neuronal Apoptosis and Enhances Spatial Learning Ability in AppTg Mice. [score:1]
f Antagomir of miR135a (AM135a) dose -dependently antagonized the effects of CEBPD. [score:1]
Attenuated CEBPD and miR-135a in Astrocytes Restores the Neuronal Neurite Outgrowth. [score:1]
Therefore, the contribution and impact of miR-135a -mediated BACE1 repression in AD patients need to be further verified. [score:1]
d CEBPD increases miR-135a promoter activities. [score:1]
Two miR-135a binding motifs were identified in Thbs1 3′UTR. [score:1]
Stable U373MG cells containing Pre-miR-135a and A-135a were generated by pLAS. [score:1]
Consistent with previous studies [46, 47], our in situ hybridization result also demonstrated that miR-135a was increased in the cortex and hippocampus of AppTg mice. [score:1]
First, we investigated the expression of miR-135a in mouse brain by in situ hybridization. [score:1]
c Antisense of miR135a (A-135a) antagonize the effects of Cebpd. [score:1]
Moreover, AM135a, the antagomir neutralizing miR-135a, could enhance THBS1 levels to prevent neuronal loss and improve the learning ability in AppTg mice. [score:1]
Luciferase activity of reporter constructs was measured after co -transfected with pre-miR-135a, CEBPD expression vectors, or treated IL-1β. [score:1]
Pre-miR-135a and Antisense of miR-135a (A-135a)-Inducible Stable Cells. [score:1]
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4
[+] score: 183
Other miRNAs from this paper: mmu-mir-200a, mmu-mir-135a-2
The role of miR-135a is rather controversial as miR-135a is upregulated in hepatocellular carcinoma promoting metastasis [16]; similarly in bladder cancer miR-135a expression is upregulated [17]. [score:9]
In this study, we have demonstrated that the expression of miR-135a was suppressed in the DSS -induced murine mo del of colitis and increased expression of miR-135a was associated with suppression of apoptosis and inflammation. [score:9]
The results showed that expression of miR-135a in colonic cells was suppressed and up -regulating miR-135a inhibited apoptosis and inflammation of colonic epithelial cells. [score:8]
Iborra et al. reported that miR-135a was down-regulated in serum in CD and UC patients, implying that miR-135a might be an important regulator in inflammatory bowel diseases [15]. [score:7]
[*] p < 0.05, [**] p < 0.01 We first predicted the candidate target gene by using TargetScan, and then confirmed that Hif1α was a target gene of miR-135a (Fig.   3a) and was also negatively regulated by miR-135a (confirmed by luciferase reporter assay, qRT-PCR, and western blot), (Fig. 3b- e). [score:7]
The results showed that miR-135a could significantly inhibit the expression of Bax, the apoptosis-promoting factor, and promote the expression of Bcl-2, the anti-apoptotic factor. [score:7]
miR-135a is associated with number of diseases including cancer [10, 11], cardiovascular diseases [12], acute lung injury [13], Alzheimer’s disease [14], CD and UC [15]. [score:7]
Thus, it can be concluded that increased expression of miR-135a and further down-regulated Hif1α is beneficial in protecting the colonic mucosa from inflammatory colitis. [score:6]
We also found that knockdown of the target gene of miR-135a, Hif1α, led to suppression of both apoptosis and inflammation. [score:6]
Additionally, Hif1α was identified as the target gene of miR-135a which promoted apoptosis and inflammation as knockdown of Hif1α led to the suppression of both apoptosis and inflammation. [score:6]
Again, similar to the effects of miR-135a, knockdown of Hif1α led to suppression of expressions of inflammatory mediators namely, IL-6 (p < 0.05), IL-8 (p < 0.01), and TNF-α (p < 0.05) compared to control group of cells (Fig. 4d). [score:5]
Murine mo del of DSS -induced colitis miR-135a Hif1α Inflammatory bowel disease Inflammatory bowel disease (IBD) is a chronic condition which is characterized by inflammatory damage to small intestine and colon; the main IBD types include ulcerative colitis (UC) and Crohn’s disease (CD) [1]. [score:5]
However, overexpression of miR-135a in the colonic cells led to suppression of apoptosis and inflammation. [score:5]
Therefore, it can be suggested that miR-135a exerts its anti-apoptotic and anti-inflammatory actions via suppressing the expression of Hif1α. [score:5]
miR-135a was down-regulated in DSS -induced colitis in mice. [score:4]
Consistently, miR-135a was significant down-regulated in colon of DSS -treated mice relative to control mice (p < 0.001). [score:4]
Up -regulating miR-135a inhibited apoptosis and inflammatory response in colonic epithelial cells. [score:4]
Hence, it can be suggested that suppression of miR-135a function leads to the development of DSS -induced colitis (as apoptosis and inflammation are the two most important factors in pathogenesis of colitis). [score:4]
Fig. 3Hif1α was a direct target gene of miR-135a. [score:4]
The expression of Hif1α was regulated by miR-135a, according to d qRT-PCR analysis and e Western blot. [score:4]
Besides, Hif1α directly targeted by miR-135a participated in the function of miR-135a in colonic epithelial cells. [score:4]
Identification of Hif1α as target gene of miR-135a. [score:3]
Similarly, several studies have also described the different expression patterns (genetic polymorphism) of different miRNAs (including miR-135a) in IBD patients and the potential role of different miRNAs in progression to colon cancer in these patients [5, 8, 9]. [score:3]
Fig. 1DSS caused symptoms of inflammation on mouse mo del and miR-135a was over-expressed in DSS -induced colitis. [score:3]
To determine expression of miR-135a, d qRT-PCR and e in situ hybridization were conducted. [score:3]
Western blot analysis revealed significant fall (p < 0.05) in Bax, a pro-apoptic factor and significant increase (p < 0.01) in the level of Bcl-2, anti-apoptic factor, (Fig. 4b and c) similarly to those seen in cells overexpressing miR-135a. [score:3]
miR-135a plays a rather contradictory role as sometimes it promote tumorigenesis and sometime suppresses it [11, 16– 19]. [score:3]
Histopathologic examination was performed and relative miR-135a expression was detected. [score:3]
Overexpression of miR-135a might be beneficial in IBD due to its anti-apoptosis and anti-inflammation effects in vitro. [score:3]
Expression of miR-135a in DSS -induced colitis. [score:3]
Similar to our findings, miR-135a suppressed apoptosis of HL-1 cells in diabetic mice [23], promoted proliferation, induced migration and tenogenic differentiation of tendon stem/progenitor cells [24], and ameliorated allergen -induced inflammation in allergic rhinitis [25]. [score:3]
Zeng Y, Liang X, Zhang G, Jiang N, Zhang T, Huang J, Zhang L, Zeng X. miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by targeting forkhead box O1. [score:3]
In colon cancer, miR-135a is known to facilitate progression of the disease [22]. [score:3]
However, in case of malignant glioma [11], epithelial ovarian cancer [18], and in lung cancer [19] miR-135a acts as a tumor suppressor. [score:3]
U6 was used as the endogenous control for miR-135a expression. [score:3]
The expression of miR-135a was decreased in the mice with DSS -induced colitis and also it was seen that apoptosis was increased in mice compared to control group of mice. [score:2]
Other studies have already mentioned the anti-apoptotic function of miR-135a. [score:1]
In situ hybridization In situ hybridization was performed with 5′-locked digoxigeninlabeled LNA™ miR-135a probe complementary to mouse mature miR-135a and LNA™ U6 snRNA as positive control (Exiqon, Vedbaek, Denmark). [score:1]
Antisense oligonucleotides (ASO)-miR-135a and its corresponding negative control (NC), i. e. ASO-NC, were all purchased from Genepharma (Shanghai, China). [score:1]
Importantly, miR-135a was found to be reduced in serum in a study of CD and UC patients [15]. [score:1]
In this study, we tried to explore the role of miR-135a in DSS -induced murine mo del of colitis. [score:1]
At the same time, we measured the expression level of miR-135a in mice by qRT-PCR and in situ hybridization (Fig. 1d and e). [score:1]
a The predicted miR-135a binding sites on Hif1α. [score:1]
Fig. 2Role of miR-135a in apoptosis and inflammation of colonic epithelial cells. [score:1]
b and c Luciferase activity in cells cotransfected with miR-135a (or ASO-miR-135a) and luciferase reporters containing Hif1α-wild type or Hif1α-mutant type vector. [score:1]
The functional role of miR-135a in DSS -induced murine colitis mo del. [score:1]
3’UTR luciferase reporter plasmids and either miR-135a mimics or ASO-miR-135a were cotransfected in colonic epithelial cells. [score:1]
At the same time, we determined the levels of TNF-α, IL-8, and IL-6 (measured by ELISA), and found that miR-135a significantly inhibited the levels of IL-6 (p < 0.05), IL-8 (p < 0.01), and TNF-α (p < 0.05) (Fig. 2d). [score:1]
In this study, we have explored the role of miR-135a in DSS -induced murine mo del of colitis. [score:1]
In this study, we aimed to explore the role of miR-135a in the etiology of colitis in murine mo del of DSS -induced colitis. [score:1]
miR-135a: microRNA-135a, Hif1α: Hypoxia-inducible factor 1-alpha. [score:1]
The recombinant vector pcDNA3 and miR-135a were constructed and after screening and identifying the recombinant, it was transfected into colonic cells. [score:1]
In order to explore the role of miR-135a in colitis, we performed flow cytometer analysis (Fig.   2a) to detect the effect of miR-135a on apoptosis of colonic epithelial cells. [score:1]
In situ hybridization was performed with 5′-locked digoxigeninlabeled LNA™ miR-135a probe complementary to mouse mature miR-135a and LNA™ U6 snRNA as positive control (Exiqon, Vedbaek, Denmark). [score:1]
miR-135a overexpresison vector was constructed using pcDNA3. [score:1]
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[+] score: 171
This overexpression resulted in the downregulation of GATA-3 mRNA and protein expression, while upregulating native miR-135a and T-box expressed in T cells (T-bet) mRNA and protein in the nasal mucosa. [score:13]
Moreover, we previously analyzed the 3′-UTR of murine GATA-3, focusing on the target sequences of the miR-135 family, using TargetScan and found a binding site specific for miR-135a, a microRNA that appears to be downregulated during AR [11]. [score:8]
indicated that our vector not only successfully transfected the nasal mucosa but also specifically infected the MCs, as shown by the overlap of miR-135a expression with expression of tryptase, a known marker of mature MCs [36, 37]. [score:5]
Overexpression of miR-135a alters T-bet and GATA-3 mRNA expression in AR mice. [score:5]
Here, these data were confirmed and we further highlighted the ability of this miR-135a to decrease GATA-3 mRNA and protein expression and increase T-bet mRNA expression in the nasal mucosa. [score:5]
This miR-135a -mediated decrease in GATA-3 expression in the positive group also appeared to reestablish the normal physiological expression of this gene as there was no significant difference between the positive and normal groups. [score:5]
In this prior work, we also overexpressed miR-135a in a mouse mo del of AR by administering a miR-135a mimic to induce native expression. [score:5]
Our decision to focus on the therapeutic potential of miR-135a stems from our previous work indicating that this miR-135a can specifically bind to GATA-3 and that overexpression of miR-135a in AR mice decreases the mRNA and protein expression of both GATA-3 and IL-4 [11]. [score:5]
As shown in Fig 8, the expression of miR-135a in the nasal mucosa after treatment with the LV miR-135a vector overlapped with expression of tryptase. [score:5]
Administration of LV miR-135a also appears to strongly suppress the allergen -induced inflammation commonly observed in AR mice, which includes increased total serum IgE concentrations, infiltration of eosinophils and MCs in the nasal mucosa, and increased GATA-3 expression, all of which returned to normal levels following treatment. [score:5]
It is likely that LV miR-135a -mediated changes in MCs via direct targeting of GATA-3. Although additional work is necessary to fully elucidate the function of miR-135a during AR, this study provides a foundation for the use of intranasally administered miRNA-containing LV vectors for treatment of allergen -induced inflammation. [score:4]
In our previous study, we found that miR-135a specifically base pairs to the 3′-UTR of GATA-3 mRNA and is downregulated during AR in our mouse mo del [12]. [score:4]
Notably, after AR mice were treated with LV miR-135a (positive group), miR-135a was significantly upregulated, indicating successful LV-host gene transduction in the nasal passages of these mice (Fig 3). [score:4]
Taking into consideration the relationship between miR-135a and GATA-3 [11] and the role of GATA-3 in MC regulation and differentiation [3, 4], we predict that miR-135a reduces MC infiltration and degranulation during AR via targeted GATA-3 binding. [score:4]
To better understand the effect of miR-135a overexpression on the nasal mucosa of AR mice, we evaluated the expression of T-bet and GATA-3 mRNA (Fig 4). [score:3]
The resolution of allergy inflammation via LV miR-135a treatment may be responsible for the beneficial effect of the treatment on lower airway disease. [score:3]
0139322.g004 Fig 4 RT-qPCR was used to determine the relative mRNA expression of T-bet and GATA-3 in the nasal mucosa of normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) mice. [score:3]
Moreover, no difference was found between the positive and normal groups, whereas the level in the normal group was significantly higher than that in the AR and negative groups, indicating that treatment with LV miR-135a restored the expression of T-bet to a normal level in AR -induced mice. [score:3]
Expression of miR-135a in the nasal mucosa of AR mice following LV infection. [score:3]
These results suggest that LV miR-135a expression is MC. [score:3]
In contrast, miR-135a expression in the negative and AR groups was significantly lower than that in the normal group and positive groups. [score:3]
Taken together, these data indicate that targeting of GATA-3 with miR-135a is an effective option for correcting the Th1/Th2 imbalance associated with acute AR. [score:3]
Effect of LV miR-135a on cytokine expression in AR mice. [score:3]
In our study, treatment the mice with LV miR-135a restored the expression of T-bet to a normal level in AR -induced mice. [score:3]
To this end, we utilized lentiviral (LV) miR-135a to infect ovalbumin (OVA)-sensitized AR mice, which were then used to determine the localization and effects of miR-135a overexpression on GATA-3 and MC in AR mice. [score:3]
Treatment with LV miR-135a strongly suppressed this allergic reaction. [score:3]
Sections were also incubated with the fluorescent nuclear dye DAPI (1:100; #C1002, Beyotime Biotech, Jiangsu, China) to determine the specific location of LV-mmu-miR-135a expression. [score:3]
Notably, a previous computational investigation utilizing bioinformatics data indicated that simplex miRNA, including those in the miR-135 family, may have the ability to regulate the immune response by targeting GATA-3 and regulating the biased differentiation of T-helper 2 (Th2) cells observed during AR [10]. [score:3]
Lentiviral-mmu-miR-135a is expressed in mast cells. [score:3]
Expression of miR-135a in the nasal mucosa of AR mice following treatment with lentiviral-mmu-miR-135a. [score:3]
RT-qPCR was used to determine the relative mRNA expression of T-bet and GATA-3 in the nasal mucosa of normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) mice. [score:3]
0139322.g008 Fig 8 (original magnification × 400) was used to analyze the expression of lentiviral-mmu-miR-135a (green; A) and tryptase (red; B) in mast cells present in the nasal mucosa of the positive group. [score:3]
The expression of miR-135a, T-bet, and GATA-3 was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). [score:3]
In the present study, we sought to identify the effects of miR-135a -mediated GATA-3 regulation on the MCs of mice with AR to further understand the pathogenesis of this common allergen -induced immune response. [score:2]
Therefore, LV miR-135a could reduce the infiltration of eosinophils and MCs in the nasal mucosa and reestablish balanced Th1/Th2 differentiation, possibly through a direct effect on ILC2s and Th2 cells. [score:2]
LV-mmu-miR-135a localization was observed in HPFs at 400 × magnification. [score:1]
was used to visualize the localization of LV-mmu-miR-135a in MCs. [score:1]
Thus, the number of MCs in the lamina propria was significantly decreased by miR-135a. [score:1]
We hypothesized that miR-135a deceased the activity of MCs; however, because the inflammatory response in the epithelial layer could still be detected, the MCs in the lamina propria were still active and migrated into the epithelial layer. [score:1]
, Ltd (permission number: SCXK-2008-0003, Wuhan, China), and divided into four experimental groups (n = 12 each): normal (control), AR (AR -induced, treated with saline), positive (AR -induced, treated with LV miR-135a), and negative (AR -induced, treated with an empty LV vector). [score:1]
Furthermore, within 3 h of each treatment on days 21–35, the AR group was treated with saline, whereas the positive and negative groups were nasally administered 2 × 10 [6] infectious units (IFUs) of LV miR-135a and 2 × 10 [6] IFUs of an empty LV vector, respectively. [score:1]
0139322.g003 Fig 3 RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups. [score:1]
Additional clinical trials utilizing LV miR-135a should be performed to determine the full therapeutic potential of this specific miRNA. [score:1]
The expression of T-bet and GATA-3 protein in CD4 [+] T cells was measured in the spleens of normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) mice using flow cytometry. [score:1]
Overall, the present study has demonstrated that LV miR-135a can be used to correct Th1/Th2 imbalances in the nasal mucosa and spleen of AR -induced mice. [score:1]
Effect of lentiviral-mmu-miR-135a on the immune response in AR mice. [score:1]
0139322.g002 Fig 2 Total serum IgE concentrations were determined for the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups 24 h after the final intranasal sensitization using ELISA. [score:1]
The LV vector containing mmu-miR-135a was constructed at the GeneChem Company (Shanghai, China). [score:1]
The toxic effects of LV miR-135a were also minimal and H&E staining of lung tissue did not show any significant histomorphological changes (S1 Fig). [score:1]
0139322.g006 Fig 6 The nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups was analyzed 24 h after the last OVA stimulation using H&E staining. [score:1]
Lentiviral-mmu-miR-135a treatment influences Th cell polarization. [score:1]
Notably, treatment with LV miR-135a in the positive group appeared to significantly decrease this percentage back to a level similar to that of the normal group. [score:1]
To further understand the role of miR-135a during AR in the present investigation, we sought to overexpress miR-135a in the nasal mucosa of AR -induced mice via intranasal infection with an LV vector containing miR-135a. [score:1]
Thus, the Th1/Th2 ratio (T-bet [+] cells/GATA-3 [+] cells) for the AR group indicates a Th2 bias, as expected, and treatment with LV miR-135a appears to decrease this ratio back to normal physiological levels. [score:1]
In our study, we found that LV miR-135a significantly decreased the number of MCs in the lamina propria tissue in the positive group, but the number of MCs in the epithelial layer was not significantly different across the AR and positive and negative groups. [score:1]
0139322.g005 Fig 5The expression of T-bet and GATA-3 protein in CD4 [+] T cells was measured in the spleens of normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) mice using flow cytometry. [score:1]
RT-qPCR was used to evaluate the relative expression levels of miR-135a in the nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups. [score:1]
Effect of LV miR-135a on serum IgE levels in AR mice. [score:1]
Laser scanning confocal microscopy was used to determine whether LV miR-135a localized specifically in the MCs of treated AR mice. [score:1]
was used to determine whether LV miR-135a localized specifically in the MCs of treated AR mice. [score:1]
Following construction, 2 × 10 [6] IFUs of the LV miR-135a were intranasally administered to mice that were fully awake in the positive group within 3 h of on days 21–35 according to a previously established protocol [13]. [score:1]
Flow cytometric analysis of Th cell polarization following LV miR-135a treatment. [score:1]
However, AR mice treated with LV miR-135a (the positive group) had levels of IgE similar to those of mice in the normal group, indicating that LV miR-135a blocks or reduces the immune response in AR mice. [score:1]
0139322.g007 Fig 7 The nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups was analyzed 24 h after the previous OVA stimulation using MC staining. [score:1]
MC localization of LV miR-135a. [score:1]
The nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups was analyzed 24 h after the previous OVA stimulation using MC staining. [score:1]
The nasal mucosa of mice in the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups was analyzed 24 h after the last OVA stimulation using H&E staining. [score:1]
Total serum IgE concentrations were determined for the normal (control), AR (AR -induced), positive (AR -induced, treated with lentiviral-mmu-miR-135a), and negative (AR -induced, treated with empty lentivirus) groups 24 h after the final intranasal sensitization using ELISA. [score:1]
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6
[+] score: 101
Other miRNAs from this paper: mmu-mir-140, mmu-mir-204, mmu-mir-135a-2
Up-regulation of miR-135a was found in colorectal adenomas and carcinomas, and suppresses the expression of adenomatous polyposis coli (APC) which is a target of miR-135a [29]. [score:10]
Our studies have shown that prolonged co-exposure with Th2 antigen and PM regulates microRNA expression with up-regulation of miR-135a. [score:7]
Our data imply that the role of AntagomiR-135a is a not only restoration of BMPR2 expression, but also has other functions to improve PAH, since miR-135a also regulates other putative target genes. [score:6]
The miR-135a is up-regulated in cancer cells and tissues, and increased expression of miR-135a promotes cells proliferation [27] and cell growth [28]. [score:6]
Our previous data showed that miR-135a expression was up-regulated in experimental PAH mice mo dels exposed to OVA & PM [8]. [score:6]
Further translation of the findings from our study is dependent on the identification of BMPR2 down-stream genes and other target genes regulated by miR-135a. [score:6]
Our study has clinically translatable implications by identifying a therapeutic target miR-135a for PAH. [score:5]
Correlation between BMPR2 expression and RVSP, and correlation between miR-135a expression and RVSP. [score:5]
Furthermore, we examined the expression of computationally identified miR-135a targets that could have a significant role for PAH. [score:5]
Therefore we hypothesized that up-regulation of miR-135a is a critical event for PAH induced by exposure to combined Th2 antigen and urban PM. [score:4]
miR-135a expression levels are a potent biomarker for PAH. [score:3]
B. RVSP and miR-135a expression are significantly correlated among mice exposed to PBS (n = 8) and mice exposed to OVA & PM (n = 9). [score:3]
AntagomiR-135a (miRCURY LNA™ microRNA inhibitor for miR-135a, 5-GGAAUAAAAAGCCAUA-3) and scrambled miRNA (5-ACGUCUAUACGCCCA-3) were purchased from Exiqon. [score:3]
We found that bone morphogenetic protein receptor type II (BMPR2) is a target of miR-135a. [score:3]
Despite the implications of miR-135a in other diseases, the role of miR-135a is still unclear in PAH. [score:3]
BMPR2 is a target of miR-135a. [score:3]
RVSPs and expression of miR-135a are significantly correlated among mice exposed to PBS and mice exposed to OVA & PM (Figure 1B). [score:3]
There are several reports showing that miR-135a is involved in the pathology of lung and heart disease such as asthma or cardiac hypertrophy. [score:3]
Furthermore, because BMPR2 is a target gene of miR-135a, we measured miR-135a expression levels in lung of mice exposed to OVA & PM. [score:3]
The miR-135a expression was increased in allergen-challenged mouse lungs in experimental asthma mo del [15]. [score:3]
BMPR2 is a target gene of miR-135a [31, 32]. [score:3]
This would be a necessary step toward evaluating miR-135a as a potential therapeutic target for the clinical management of PAH. [score:1]
Our data are further supported by other work indicating that miR-135a was increased in the lungs of antigen-exposed, sensitized mice [15]. [score:1]
Reducing miR-135a by AntagomiR-135a attenuated and prevented developing PAH induced by OVA & PM in this study. [score:1]
Specially, miR-135a could serve as biomarkers helping to manage PAH. [score:1]
Decreased cardiac myosin binding protein C (MYBPC3) by miR-135a resulted in hypertrophy of the muscle and heart failure [24]. [score:1]
We also showed that miR-135a levels returned to near baseline levels by neutralizing IL-13 and IL-17A [8]. [score:1]
Reducing miR-135a by AntagomiR-135a attenuated PAH phenotypes induced by OVA & PM. [score:1]
We found that miR-135a levels were significantly increased in the lungs of OVA & PM exposed mice. [score:1]
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[+] score: 96
Changes in miRNA expression at 3 h ranged from 11-fold down-regulation (miR-224) to 3.8-fold up-regulation (miR-367), and at 24 h from 7-fold down-regulation (miR-222) to 20.6-fold up-regulation (miR-135a*; Figure 2). [score:15]
Down-regulated miR-135a* target genes are listed in Table 4. Canonical pathway analysis of these genes showed that the expression of genes linked to the production of nitric oxide (NO) and reactive oxygen species (ROS; Ncf2 and Ppp2r2b), Wnt/β-catenin signaling (Wnt1), and ERK/MAP kinase signaling (Rapget3) could be down-regulated by miR-135a* in response to NP exposure Table 3 Functional classification of miR-135a* target genes Molecular and cellular functions Name P-value No. [score:13]
Down-regulated miR-135a* target genes are listed in Table 4. Canonical pathway analysis of these genes showed that the expression of genes linked to the production of nitric oxide (NO) and reactive oxygen species (ROS; Ncf2 and Ppp2r2b), Wnt/β-catenin signaling (Wnt1), and ERK/MAP kinase signaling (Rapget3) could be down-regulated by miR-135a* in response to NP exposure Table 3 Functional classification of miR-135a* target genes Molecular and cellular functions Name P-value No. [score:13]
miR-135a* was significantly up-regulated after exposure to NP for 24 h. The change in miR-135a* expression was the highest in this study (20.6-fold up-regulation). [score:9]
of genes Cell Cycle 2.48E-04 - 1.72E-02 7 Cell Death 1.02E-03 - 4.78E-02 7 Cell Morphology 1.02E-03 - 4.69E-02 3 Cell-To-Cell Signaling and Interaction 1.02E-03 - 4.78E-02 4 Cellular Assembly and Organization 1.02E-03 - 4.00E-02 2 Table 4 miR-135a* target genes the expression of which was down-regulated in NP -treated TM4 cells Gene symbol Gene title Acc. [score:8]
of genes Cell Cycle 2.48E-04 - 1.72E-02 7 Cell Death 1.02E-03 - 4.78E-02 7 Cell Morphology 1.02E-03 - 4.69E-02 3 Cell-To-Cell Signaling and Interaction 1.02E-03 - 4.78E-02 4 Cellular Assembly and Organization 1.02E-03 - 4.00E-02 2 Table 4 miR-135a* target genes the expression of which was down-regulated in NP -treated TM4 cells Gene symbol Gene title Acc. [score:8]
qRT-PCR results showed that miR-135a* was up-regulated 1.9-fold and miR-199a-5p down-regulated approximately 1.7-fold in independent experiments (Additional file 2, Figure S2). [score:7]
We chose miR-135a* and miR-199a-5p, two miRNAs that were found in microarray analyses to be highly up- and down-regulated, respectively. [score:4]
Finally, miR-135a* target gene analysis suggests that the generation of reactive oxygen species (ROS) following exposure to NP exposure may be mediated by miR-135a* through regulation of the Wnt/beta-catenin signaling pathway. [score:4]
Functional analysis of miR-135a* target genes. [score:3]
miR-135a* may target ERK/MAP kinase signaling-related genes. [score:3]
Genes implicated in the production of NO and ROS were predicted to be miR-135a* targets. [score:3]
Levels of expression of the miRNAs miR-135a* and miR-199a-5p were validated by qRT-PCR. [score:3]
Click here for file Supplemental Figure S2: Validation of miR-135* and miR-199a-5a levels by qRT-PCR. [score:1]
Supplemental Figure S2: Validation of miR-135* and miR-199a-5a levels by qRT-PCR. [score:1]
We thus suggest that miR-135a* may play important roles following NP exposure. [score:1]
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8
[+] score: 57
High mRNA and protein expression levels of miR-135a and low mRNA and protein expression levels of GATA-3 and IL-4 in the nasal mocosa following miR-135a mimic intervention. [score:5]
By using a miR-135a mimic and a mimic control in the nasal mucosa of the mice, the expression levels of miR-135a were significantly higher, and the expression levels of GATA-3 and IL-4 were significantly lower in the mimic group than those of the mimic control and AR groups. [score:5]
TargetScanMouse, an online bioinformatics program, was used analyze the 3′ UTR of GATA-3 and the miR-135a 3′ UTR, and thus to predict the consequential pairing of the target region and miRNA (Fig. 1) according to the method described previously (16). [score:5]
It was also found that the targets of the miR-135a 3′ UTR included the 3′ UTR of GATA-3. The expression levels of miR-135a in the nasal mucosa of the AR mice were significantly lower than those of the control group (Fig. 2). [score:5]
However, the mimic control and AR groups had significantly lower expression levels of miR-135a and higher expression levels of GATA-3 and IL-4 compared with those of the control group (Fig. 3). [score:4]
It was demonstrated that the miR-135a mimic reduced the serum OVA-sIgE concentration, and downregulated the mRNA and protein levels of GATA-3 and IL-4. Furthermore, the miR-135a mimic caused the mRNA and protein levels of T-bet and IFN-γ to increase in the nasal mucosa. [score:4]
The expression levels of miR-135a, GATA-3 and IL-4 in the nasal mucosa of the mimic control group were not significantly different from those of the AR group. [score:3]
In the nasal mucosa of the control, mimic, mimic control and AR groups, Bulge-Loop™ miRNA qPCR was used to detect the miR-135a expression levels, and U6 small nuclear RNA was used as an internal control (Guangzhou RiboBio Co. [score:3]
Therefore, the present study analyzed the 3′ UTR of mouse GATA-3 and miR-135 with TargetScan. [score:3]
Low expression levels of miR-135a in the nasal mucosa of AR mice. [score:3]
High mRNA and protein expression levels of T-bet and IFN-γ in the nasal mucosa following miR-135a mimic intervention. [score:3]
Thus, treatment with miR-135a was effective in AR and may provide a basis for miRNA application towards novel genetic treatments for allergic diseases. [score:3]
The results indicated one or several miRNA candidates were involved in the regulation of Th2 cell differentiation through GATA-3. In the present study, it was demonstrated that GATA-3 and miR-135a were specifically binding to each other, suggesting that miR-135a may play a role in affecting the Th1/Th2 imbalance in AR mice. [score:2]
Following intervention with a miR-135a mimic and a mimic control, it was demonstrated that the serum OVA-sIgE concentration in the mimic group was significantly lower than that in the mimic control and AR groups, but with no significant difference to that of the control group. [score:1]
These results further indicated that treatment with miR-135a was effective for correcting the Th1/Th2 imbalance in AR mice. [score:1]
Overall, this study showed that a miR-135a mimic corrected the imbalance of Th1/Th2 in the nasal mucosa of AR mice. [score:1]
AR intervention by a miR-135a mimic and mimic control. [score:1]
By using Mouse, it was found that the sequence 5′-AAGCCAU-3′ of the 3′ UTR of GATA-3, at the sites of 222–228, had specific binding sites with the 3′-UUCGGUA-5′ of miR-135a. [score:1]
Low serum OVA-sIgE concentration in mice following AR intervention using a miR-135a mimic. [score:1]
To test this hypothesis, a miR-135a mimic and a mimic control were used in the present study. [score:1]
On days 14, 16, 18 and 20, the mimic group was treated intranasally with 20 μl saline containing 50 μg miR-135a mimic to intervene with the incidence of AR, while the mimic control group was treated under identical conditions with an arbitrary sequence as previously described (23). [score:1]
The miR-135a mimic sequence was as follows: 5′-UAUGGCUUUUUAUUCCUAUGUGA-3′; and the the mimic control sequence was as follows: 5′-UUUGUACUA CACAAAAGUACUG-3′ (Guangzhou RiboBio Co. [score:1]
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9
[+] score: 44
In miR-153 transfected ALCs compared with negative control siRNA transfected ALCs, the expression of miR-3085 and miR-346 was upregulated, while the expression of miR-298, miR-135a, miR-376b and miR-203 was downregulated. [score:10]
Specifically, in miR-153 transfected ALCs, the expression of miR-3085 and miR-346 was upregulated compared with negative control siRNA, while the expression of miR-298, miR-135a, miR-376b and miR-203 was downregulated (P < 0.05) (Fig. 3b and). [score:10]
In LS8 cells, the increased intracellular level of miR-153 induced similar directional changes (as in ALCs) in the expression of miR-3085, miR-298, miR-135a and miR-376b. [score:4]
In both ALCs (a) and LS8 cells (b), treatment with EMD elicited significant downregulation of miR-3085, miR-298, miR-138, miR-135a and miR-376b. [score:4]
Within both ALCs and LS8 cells, addition of EMD elicited significant downregulation of miR-3085, miR-298, miR-138, miR-135a and miR-376b (P < 0.05) (Fig. 6a,b and). [score:4]
In LS8 cells, intracellular overloading of miR-153 induced similar changes in the expression of miR-3085, miR-298, miR-135a and miR-376b as those in ALCs. [score:3]
Additionally, miR-31, miR-21, miR-135a, miR-138, miR-203 and miR-346 showed significantly differential expression patterns between ALCs and LS8 cells (P < 0.05) (Fig. 3a and). [score:3]
MiR-31, miR-21, miR-135a, miR-138, miR-203 and miR-346 showed statistically significant differential expression between the two ameloblast-like cell mo dels. [score:3]
In the significantly enriched functional categories, such as those labeled with ‘endosome membrane’ or ‘lysosomal lumen’, miR-153 together with miR-3085, miR-298, miR-138, miR-135a, miR376b, miR-203 and miR-346 were predicted to be epigenetic regulators involved in endocytosis and endosomal/lysosomal pathways 11. [score:2]
In order to identify that ALCs and LS8 cells are suitable mo dels for investigating the functional role of miR-153, the baseline expression of miR-153 (along with miR-31, miR-21, miR-223, miR-410, miR-3085, miR-298, miR-135a, miR-138, miR376b, miR-203 and miR-346) was quantified by real-time PCR. [score:1]
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10
[+] score: 43
These included FASL IL18RAP, and KITL, which are targets of miR-377; IL25 IL12A TNFSF14, and CLCF1, which are targets of miR-691; CCR10, a target of miR-1935; CXCL16, a target of miR-190; IL24 IFNG CXCL16, and CD40LG, targets of miR-135a*; IL18R1 CD40 CXCL12, and CSF, targets of miR-290-5p; and IL24 XCL1, and IL12B, targets of miR-203 (Table 1). [score:15]
In this study, the target genes of modulated miRNAs were found to be involved in Jak-STAT signaling, including JAK2 SOCS4, which are targets of miR-377; TYK2 and IL12A, targets of miR-691; IL6, a target of miR-190; IFNAR2, a target of miR-135a*; IFNGR2 and AKT1, targets of miR-290-5p; and SOCS3 and AKT2, targets of miR-203. [score:15]
As shown in Table 1, the predicted target genes of six up-regulated miRNAs, miR-691, miR-377, miR-1935, miR-190, miR-203, and miR-135a*, and one down-regulated miRNA, miR-145, were found to be involved in immune-related pathways, such as the Jak-STAT signaling pathway, MAPK signaling pathway, Fc gamma R -mediated phagocytosis and cytokine-cytokine receptor interactions. [score:9]
As shown in Figure 2B, nine miRNAs, miR-691, miR-377, miR-1935, miR-190, miR-1902, miR-135a*, miR-203, miR-2138, and miR-290-5p, were found to be significantly up-regulated. [score:4]
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11
[+] score: 37
For example, the targets of the mir-135 family, a family that was up-regulated in the vestibule, were enriched in a set of proteins down-regulated in this tissue; and the targets of mir-205, a miRNA that exhibited a higher expression in the cochlea, were depleted in a set of proteins also up-regulated in the cochlea. [score:16]
We noted that targets of mir-135 were marginally enriched in the set of all proteins up-regulated in the cochlea (P = 0.075), and a statistically significant enrichment was found only when considering genes up-regulated in the cochlea only on the protein level (i. e., genes without significant mRNA changes between the two tissues, P = 0.047). [score:9]
Thus, for six miRNA families – mir-135, mir-205, mir-142-3p, mir-15/16, mir-218 and mir-24 - we obtained evidence for their functional relevance in the inner ear on two levels: (a) the miRNAs were differentially expressed between the two tissues; and (b) their predicted targets were differentially expressed in a manner consistent with the currently accepted mo del of miRNA regulation. [score:8]
Due to the similarity between miR-135b and miR-135a, we predict that miR-135a also regulates PSIP1-P75 in the vestibular system. [score:2]
According to our results, miR-135a also has a higher level of expression in the vestibular as compared to the cochlear sensory epithelia. [score:2]
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12
[+] score: 19
We found that the three ethanol-sensitive miRNAs with the highest average expression fold changes in the hippocampus, including the well-conserved miR-135a and miR-135b, were also significantly up-regulated in serum. [score:6]
Of the remaining validated ethanol-sensitive miRNAs, miR-135a and miR-135b are well-conserved and predicted to target Complexin 1 and Complexin 2 (TargetScan, Release 6.2), which are involved in modulating neurotransmitter release [40]. [score:5]
Four out of seven miRNAs, miR-135a, miR-135b, miR-467b-5p and miR-487b, were confirmed to be significantly up-regulated in ethanol-exposed mice (Fig.   4c). [score:4]
Three miRNAs, miR-135a, miR-135b and miR-467b-5p, were significantly up-regulated (≥twofold) in the ethanol-exposed group compared to controls (Fig.   5). [score:3]
Linear regression analysis showed significant linear relationships between the hippocampus and serum for miR-135a (R [2] = 0.84, P < 0.01), miR-135b (R [2] = 0.91, P < 0.001) and miR-467b-5p (R [2] = 0.60, P < 0.05) in ethanol-exposed mice only. [score:1]
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13
[+] score: 17
These data confirm that miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b target endogenous SIRT1 and downregulate its expression. [score:8]
Specifically, SIRT1 expression is repressed by miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b. [score:3]
Overexpression of miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b decreased SIRT1 protein levels in mESCs (Figure 4B). [score:3]
miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b target endogenous SIRT1. [score:3]
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14
[+] score: 16
Furthermore, qPCR was performed again to validate the downregulated and upregulated expression of selected miRNAs that may be relevant to development and confirmed that miR-135, miR-302, miR-449a, miR-200b, miR-200c, miR-193b, miR-130, and miR-141 were downregulated, whereas miR-10a, miR-181, and miR-470 were upregulated by RA treatment (Fig 4C and 4D). [score:16]
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15
[+] score: 16
In addition, PRP19beta, another miR-135 target gene, was founded to inhibit neurons differentiation and stimulate glial cells growth [35]. [score:5]
Recently, one study confirmed that Siah, a predicted target of the miR-135 family, regulated neuronal migration, development of nervous system and morphogenesis of the brain by inducing Pard3A protein ubiquitination [34]. [score:5]
To further illuminate the possible roles of miR-135b and miR-708 in the pathogenesis of AD, Gene Ontology (GO) enrichment for biological processes and molecular functions of miR-135 and miR-708 targets were performed. [score:3]
It is reported that miR-135b, one important member of the miR-135 family, played essential roles in development of many tumors, such as anaplastic large cell lymphoma [31], osteosarcoma [32] and colon cancer [33]. [score:2]
The results revealed that miR-135 was related to DNA recombination, protein ubiquitination, protein amino acid autophosphorylation and transcription factor binding (Table 2). [score:1]
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16
[+] score: 15
mmu-miR-142-3p mmu-miR-152 mmu-miR-135b mmu-miR-135a mmu-miR-34c mmu-miR-494 MicroCosm Bmal1 Bmal1, Rorβ - - Reverbα Bmal1, Rorβ TargetScan Bmal1 - - - - Bmal1, Clock MiRanda Bmal1 Bmal1, Rorα, Rorβ Rorα, Rorβ Rorα, Rorβ Per2 Bmal1, Per2, Rorβ Because recent findings indicate that despite their abundant expression in the cytoplasm, 18s and 28s rRNA are absent in RNA extracted from circulating exosomes [31], 18s rRNA levels were analyzed in serum and WBC fractions of blood samples collected from mice (n = 3–4) at ZT3 and ZT7 to confirm that the detected small RNAs reflect serum expression, rather than artifact associated with cellular lysis during sample preparation. [score:7]
mmu-miR-142-3p mmu-miR-152 mmu-miR-135b mmu-miR-135a mmu-miR-34c mmu-miR-494 MicroCosm Bmal1 Bmal1, Rorβ - - Reverbα Bmal1, Rorβ TargetScan Bmal1 - - - - Bmal1, Clock MiRanda Bmal1 Bmal1, Rorα, Rorβ Rorα, Rorβ Rorα, Rorβ Per2 Bmal1, Per2, Rorβ Because recent findings indicate that despite their abundant expression in the cytoplasm, 18s and 28s rRNA are absent in RNA extracted from circulating exosomes [31], 18s rRNA levels were analyzed in serum and WBC fractions of blood samples collected from mice (n = 3–4) at ZT3 and ZT7 to confirm that the detected small RNAs reflect serum expression, rather than artifact associated with cellular lysis during sample preparation. [score:7]
miR-142-3p, miR-152, miR-494, miR-135b, miR-135a and miR-34c were found in descending order of abundance in the serum (Fig. 1A). [score:1]
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17
[+] score: 13
Mature ID Fold Regulation miR-135b −2.6965 miR-363 −2.5995 miR-98 −2.543 miR-132 −2.355 miR-103 −2.1776 miR-99b −2.044 miR-135a −1.8734 let-7d −1.7861 miR-130a −1.6538 miR-152 −1.6246 miR-129-5p −1.6232 miR-298 −1.6169 miR-185 −1.6035 miR-214 −1.5746 miR-140 −1.5688 miR-134 −1.5667 miR-18b −1.5607 miR-194 −1.5509 let-7f −1.5107 miR-149 −1.51 A. Scatterplot showing relative expression of miRNAs by macroarray. [score:4]
Mature ID Fold Regulation miR-135b −2.6965 miR-363 −2.5995 miR-98 −2.543 miR-132 −2.355 miR-103 −2.1776 miR-99b −2.044 miR-135a −1.8734 let-7d −1.7861 miR-130a −1.6538 miR-152 −1.6246 miR-129-5p −1.6232 miR-298 −1.6169 miR-185 −1.6035 miR-214 −1.5746 miR-140 −1.5688 miR-134 −1.5667 miR-18b −1.5607 miR-194 −1.5509 let-7f −1.5107 miR-149 −1.51 Because miRNAs typically regulate translation in animal cells, we compared CXCL10 and STAT1 protein levels in both control and Dicer [d/d] animals and cells. [score:4]
It remains of course possible that other miRNAs, such as miR-210, miR-135a/b or miR-16, could also be involved in the regulation of this chemokine. [score:2]
Thus, Cxcl10 and miR-210, miR135a/b, or Oas2 and miR-7d, miR-140, miR-98, let-7f, displayed opposite regulation in Dicer mutant cells, and may be involved in the same networks in vivo. [score:2]
As stated above, the miRanda algorithm predicted binding sites for numerous miRNAs, including miR-210 and miR-135a/b. [score:1]
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18
[+] score: 12
This work is important to our study because miR-135a downregulates APC gene expression [43, 44] and thus may be responsible affecting chemotherapeutic resistance in our mo del systems. [score:6]
Another important factor is miR-135a, which binds to the APC gene [43, 44], and inhibits STAT3 -induced pro survival gene expression and induces apoptosis in gastric cancer and lymphoma [45]. [score:5]
Recently work has also shown that miR-135a contributes to paclitaxel resistance in vitro in cell culture mo dels for non-small cell lung cancer, breast cancer and ovarian cancer while in vivo work with a non-small cell lung cancer mo del demonstrated a similar response [44]. [score:1]
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[+] score: 10
Among the other novel predictions, (miR-135a, -203, -335, -338-3p and -93), miR-335 that has two binding sites on the 3'UTR of Hif-1a was found to be the most promising regulator of Hif-1a expression (Fig 2). [score:4]
Among the 10 miRNAs, interaction of miR-17, -18a, -20a and -20b-5p with HIF-1a had been reported previously in cancer pathogenesis [16, 22] whereas the remaining six miRNAs, miR-135a/b, -203, -335, -338-3p and -93 had not been validated in any disease condition. [score:3]
miR-135a, -203 and -338-3p did not show direct interaction with Hif-1α (Fig 2B). [score:2]
As miR-135a and miR-135b only differs by one nucleotide in a non-seed region, miR-135a was selected for validation studies. [score:1]
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[+] score: 10
Evidence of the concerted interplay of miRNAs regulated by CpG-ODN and their potential target mRNAs was observed (Fig. 4) for 2 miRNAs upregulated (hsa-miR-302b and hsa-miR-374b) and for 13 miRNAs downregulated in CpG-ODN -treated mice (hsa-miR-135a, hsa-miR-136, hsa-miR-340, hsa-miR-445-5p, hsa-miR-424, hsa-miR-96, hsa-miR-142-3p, hsa-miR-140-5p, hsa-miR-542-3p, hsa-miR-18a, hsa-miR-18b, hsa-miR-101, and hsa-miR-99a). [score:10]
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21
[+] score: 10
Next to miR-204, the next most highly expressed MG miRNAs (with less than 20% expression in neurons) were miR-125b, and miR-9. These two miRNAs are also highly expressed in P7 FAC-sorted astrocytes of the forebrain, along with several others of the most highly expressed mGliomiRs (miR-99a, miR-204, miR-135a) and shared miRs (miR-720, let-7b, miR-29a, and miR-30d) 40. [score:9]
For the other mGliomiRs, miR-135a 40 51, miR-23a 45, and miR-99a 40 have been reported in astrocytes as well as for Schwann cells in the sciatic nerve along with miR-100 48, indicating that these miRNAs could be common among glia. [score:1]
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[+] score: 9
In mouse ST2 MSCs, miR-125b inhibited osteoblast differentiation while miR-133 and miR-135 directly targeted Runx2 and Smad5 production, inhibiting the commitment of C2C12 MSCs into bone precursor cells [14], [15]. [score:8]
Although it has been reported that a number of miRNAs, miR-204/211 [13], miR-125b [14], miR-133 and miR-135 [15], miR-141 and miR-200a [16], and miR-29b [17], were involved in osteoblastic differentiation, a few papers have been reported with regard to the functions of miR-10a, miR-10b, miR-9-3p and miR-19b. [score:1]
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23
[+] score: 9
REST directly down-regulates a large number of genes at the transcriptional level, but also probably indirectly activates the expression of other genes at the post-transcriptional level via the repression of many noncoding targets (Conaco et al., 2006; Mortazavi et al., 2006; Wu and Xie, 2006; Visvanathan et al., 2007; Singh et al., 2008; Johnson et al., 2009), including several micro RNAs (miRNAs) considered to be brain-specific (such as miR9, miR124, miR132, miR135, miR139, and miR153; Figure 1). [score:9]
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[+] score: 9
Other miRNAs from this paper: mmu-mir-135a-2
Lung expression of miR-135a was significantly increased in antigen and PM [2.5] exposed wild type mice, as expected [16], and in B cell KO mice that were injected with antigen-specific IgG1 during antigen and PM [2.5] challenge (Fig 5F). [score:3]
The inflammatory marker [48], miR-135a, was studied next because it is inhibited by co-neutralization of IL-13 and IL-17A in the lungs of wild type mice exposed with antigen and PM [2.5] [16]. [score:3]
The microRNA (miR)-135a expression level was determined by using miR-135a with LNA -modified primers (Exiqon) and SYBR Green master mix (Exiqon) with these conditions: 95°C for 10 min, followed by 45 cycles of 95°C for 10 s and 60°C for 1 min, followed by a hold at 4°C. [score:2]
In contrast, the expression of miR-135a in the lungs of control B cell KO mice (challenged with antigen and PM [2.5] with no injection of antigen-specific IgG1) was not increased when compared to saline (Fig 5F) and significantly lower when compared to wild type animals challenged with antigen and PM [2.5] (Fig 5F). [score:1]
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[+] score: 8
For instance, miR-135a/b are downregulated in cisplatin resistance (A549/DDP) cells, and the overexpression of miR-135a/b sensitizes A549/DDP cells to cisplatin by targeting MCL1 (myeloid cell leukemia 1) [15]. [score:8]
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[+] score: 8
A recent study reported that miR-181a and b, miR-199b, miR-135a and miR-205 targeted endogenous SIRT1 and downregulated its expression in mouse embryonic stem cells [28]. [score:8]
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27
[+] score: 7
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-15a, hsa-mir-18a, hsa-mir-21, hsa-mir-27a, hsa-mir-96, hsa-mir-99a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30b, mmu-mir-99a, mmu-mir-124-3, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-181a-2, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-181a-1, hsa-mir-200b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, mmu-mir-200a, 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-15a, mmu-mir-18a, mmu-mir-21a, mmu-mir-27a, mmu-mir-96, mmu-mir-135b, mmu-mir-181a-1, mmu-mir-199a-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-200a, hsa-mir-135b, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-15a-1, dre-mir-15a-2, dre-mir-18a, dre-mir-21-1, dre-mir-21-2, dre-mir-27a, dre-mir-27b, dre-mir-27c, dre-mir-27d, dre-mir-27e, dre-mir-30b, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-125b-1, dre-mir-125b-2, dre-mir-125b-3, dre-mir-135c-1, dre-mir-135c-2, dre-mir-200a, dre-mir-200b, dre-let-7j, dre-mir-135b, dre-mir-181a-2, dre-mir-135a, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
An example of such a miR-target pair is miR-135 and Psip, PC4- and SF-2 interacting protein/Ledgf (Elkan-Miller et al, 2011), which has been implicated in transcriptional regulation of stress-related genes, having an anti-apoptotic effect, involved in mRNA splicing, cell survival and is part of a fusion gene in leukaemia. [score:4]
miR-135 is reduced in the cochlear hair cells, while its expression is high in vestibular hair cells. [score:3]
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28
[+] score: 7
Moreover, some differentially up-regulated microRNAs (such as miR-466h-5p, miR-135a-1*, miR-2137, miR-223, miR-139-5p, miR-29b-1*, and miR-7a) displayed earlier in PR8 infected lungs than in BJ501 infected lungs. [score:4]
There was no target for mmu-miR-1, mmu-miR-135a-1, mmu-miR-2145, mmu-miR-24-2 or mmu-miR-29b-1 in the database. [score:3]
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[+] score: 7
Deletion of the miR-221/222 binding site in the Angptl2-3′UTR reporter (Fluc-Angptl2-3'UTR-Δ 221/222) was performed using a PrimeSTAR mutagenesis basal kit (Takara Bio) according to the manufacturer's instructions miR-221, miR-222, miR-211, miR-204 or miR-135a overexpression vectors were constructed by inserting sequences including the full-length mature microRNA sequences into pBApo-CMV (Takara Bio). [score:3]
Relative luciferase activity in NRCMs harbouring the reporter and transfected with control pcDNA3.1 vector or miR-221, miR-222, miR-211, miR-204 or miR-135a expression vectors. [score:3]
org database identified five candidates, including miR-135a, miR-204, miR-211, miR-221 and miR-222, predicted to bind to the Angptl2 mRNA 3′UTR. [score:1]
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30
[+] score: 7
Previous studies have identified Wnt/β-catenin signaling as a direct and functional target of several miRNAs, such as miR-200a, miR-135a, miR-30–5p and miR-612 [16, 17, 20, 21]. [score:4]
As a result, transfection of miR-200a and miR-135a mimics could inhibit the reporter activity (Data not shown), which is consistent with previous reports [16, 17]. [score:3]
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31
[+] score: 6
Linc-MD1 can sponge miR-133 and miR-135 away from their target mRNAs, thus upregulating MAML1 and MEF2C, respectively [58]. [score:6]
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[+] score: 6
MicroRNA-135a and -200b, potential Biomarkers for Alzheimers disease, regulate β secretase and amyloid precursor protein. [score:3]
Beta-secretase 1 (BACE-1) and APP, which play important roles in AD, were identified as the targets of miR-135a and miR-200b, respectively (Liu et al., 2014). [score:3]
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33
[+] score: 6
Recently, several miRNAs including miR-181a and b, miR-9, miR-204, miR-199b, and miR-135a were shown to down-regulate SIRT1 expression in mESC [22]. [score:6]
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34
[+] score: 6
The dysregulation of miRNAs in CRC has been reported using miRNA expression profiling studies with different miRNAs identified either as enhancers (miR-21, miR-31, miR-103, miR-107) or suppressors (miR-135, miR-145, miR-200c) in the initiation and evolution of tumor metastasis [8- 13]. [score:6]
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35
[+] score: 5
The results given in Table S1 show that expressions of miR-100, miR-125b, miR-135a, miR-138, miR-150, miR-146a, miR-221 which were decreased in HD cell mo del [33] were also decreased in and the expressions of miR-127-3p and miR-214 were increased in both STHdh [Q111]/Hdh [Q111] cells [33] and the R6/2 mouse mo del. [score:5]
[1 to 20 of 1 sentences]
36
[+] score: 5
Other miRNAs from this paper: mmu-mir-135a-2
The dysfunction of posttranscriptional regulation, such as the abnormal HOXA10 methylation [19] and dysregulation of miR-135a/b [20], was reported to contribute to decrease HOXA10 expression in the endometrium of ENDO women 13, 21. [score:5]
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37
[+] score: 5
Expression of miR-467a*, interestingly, was enriched only in the nucleus of LSK and promyelocytes, while expression of miR-135* and miR-142-3p did not appear to be nuclear-enriched in any myeloid population (Figure 5B). [score:5]
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38
[+] score: 5
For instance, linc-MD1 is a muscle-specific intergenic lncRNA that acts as a sponge for miR-133 and miR-135, preventing their suppression of MAML1 and MEF2C and activating muscle-specific gene expression [6]. [score:5]
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39
[+] 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-21, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-33a, hsa-mir-98, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-133a-1, mmu-mir-141, mmu-mir-194-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-203a, hsa-mir-211, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-200b, mmu-mir-300, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-141, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, 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-21a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-343, rno-mir-135b, mmu-mir-135b, hsa-mir-200c, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-33, mmu-mir-211, mmu-mir-29b-2, mmu-mir-135a-2, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-326, hsa-mir-135b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, 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-21, rno-mir-26b, rno-mir-27b, rno-mir-27a, rno-mir-29b-2, rno-mir-29a, rno-mir-29b-1, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-33, rno-mir-98, rno-mir-126a, rno-mir-133a, rno-mir-135a, rno-mir-141, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-203a, rno-mir-211, rno-mir-218a-2, rno-mir-218a-1, rno-mir-300, hsa-mir-429, mmu-mir-429, rno-mir-429, hsa-mir-485, hsa-mir-511, hsa-mir-532, mmu-mir-532, rno-mir-133b, mmu-mir-485, rno-mir-485, hsa-mir-33b, mmu-mir-702, mmu-mir-343, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, hsa-mir-300, mmu-mir-511, rno-mir-466b-1, rno-mir-466b-2, rno-mir-532, rno-mir-511, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466b-8, hsa-mir-3120, rno-mir-203b, rno-mir-3557, rno-mir-218b, rno-mir-3569, rno-mir-133c, rno-mir-702, rno-mir-3120, hsa-mir-203b, mmu-mir-344i, rno-mir-344i, rno-mir-6316, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-3569, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, rno-mir-466b-3, rno-mir-466b-4, mmu-mir-203b
Cesana et al. showed that a long-intergenic ncRNA (lincRNA), linc-MD1, regulates muscle differentiation by interacting with two miRNAs, miR-135 and miR-133, which can bind to MAML1 and MEF2C to regulate their expression levels. [score:5]
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[+] score: 4
Mmu-miR-135a ectopically overexpressed with a lentivirus in tooth germ during the cap stage, revealed that Bmp signaling, specifically Bmpr-Ia and Bmpr-Ib, regulates tooth formation in conjunction with this miRNA [25]. [score:4]
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[+] score: 4
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-15a, hsa-mir-17, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-9-2, mmu-mir-137, mmu-mir-140, mmu-mir-150, mmu-mir-155, mmu-mir-24-1, mmu-mir-193a, mmu-mir-194-1, mmu-mir-204, mmu-mir-205, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-143, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-222, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-143, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-150, hsa-mir-193a, hsa-mir-194-1, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, 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-15a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-34a, rno-mir-322-1, mmu-mir-322, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-140, rno-mir-350-1, mmu-mir-350, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-33, mmu-mir-222, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-375, mmu-mir-375, mmu-mir-133b, hsa-mir-133b, 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-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-19b-1, rno-mir-19b-2, rno-mir-23a, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-27b, rno-mir-29a, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-31a, rno-mir-32, rno-mir-33, rno-mir-34a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-106b, rno-mir-126a, rno-mir-135a, rno-mir-137, rno-mir-143, rno-mir-150, rno-mir-193a, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-204, rno-mir-205, rno-mir-222, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, mmu-mir-410, hsa-mir-329-1, hsa-mir-329-2, mmu-mir-470, hsa-mir-410, hsa-mir-486-1, hsa-mir-499a, rno-mir-133b, mmu-mir-486a, hsa-mir-33b, rno-mir-499, mmu-mir-499, mmu-mir-467d, hsa-mir-891a, hsa-mir-892a, hsa-mir-890, hsa-mir-891b, hsa-mir-888, hsa-mir-892b, rno-mir-17-2, rno-mir-375, rno-mir-410, mmu-mir-486b, rno-mir-31b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-499b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, hsa-mir-486-2, mmu-mir-126b, rno-mir-155, rno-let-7g, rno-mir-15a, rno-mir-196b-2, rno-mir-322-2, rno-mir-350-2, rno-mir-486, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
The prospect that a similar function may extend to other miRNAs is suggested by the conservation of several miRNAs (e. g. miR-25, miR-34a/b/c, miR-135a/b, miR-194, and miR-200a) that are capable of directly targeting the Wnt/β-catenin, a signaling pathway that has been wi dely implicated in the control of oncogenic hallmarks such as cell proliferation, metastasis, angiogenesis, telomerase activity, and apoptosis (reviewed by [49]). [score:4]
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[+] score: 4
To explore whether other miRNAs and genes involved in germ cell development were altered in PGCs as consequence of VCZ exposure, we examined the expression of miR-21, miR-135*, miR-381 and miR-486 miRNAs. [score:4]
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43
[+] score: 4
Other miRNAs from this paper: mmu-mir-16-1, mmu-mir-16-2, mmu-mir-135b, mmu-mir-135a-2
15, 46 Hence, miR-135 levels were upregulated after single and chronic FLX administrations, [47] suggesting that this microRNA may act as an endogenous homeostatic mechanism to maintain the physiological balance between SERT and 5-HT [1A]-autoreceptors. [score:4]
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[+] score: 4
Agarwal P. Srivastava R. Srivastava A. K. Ali S. Datta M. (2013) miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle. [score:4]
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45
[+] score: 4
A muscle-specific lncRNA, linc-MD1, displays decoy activity for two specific miRNAs (miR-133 and miR-135) and regulates the expression of MAML1 and MEF2C in a molecular circuitry affecting the differentiation program [28]. [score:4]
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46
[+] score: 4
QRT-PCR analysis revealed that miRNAs classified within the degenerative group, namely miR-1, miR-29b, miR-29c, and miR-135a (Greco et al., 2009) were expressed in similar manner in diaphragm muscle of both mdx and mdx/mIGF-1 mice (Figure 2A). [score:3]
Dystrophic-signature miRNAs has been divided into three main classes: degenerative miRNAs (miR-1, miR-29c, and miR-135a), regeneration miRNAs (miR-31, miR-34c, miR-206, miR-335, miR-449, and miR-494), and inflammatory miRNAs (miR-222 and miR-223) (Greco et al., 2009). [score:1]
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47
[+] score: 4
miR-135a/b was also highly upregulated and is known to be a potent inducer of Wnt pathway activity [32]. [score:4]
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48
[+] score: 4
Neither the putative miR-135 binding sites in the second exon of linc-MD1, nor the described distal or proximal regulatory elements [9], identified by myogenin or myoD ChIP-seq approaches in C2C12 myocytes [8, 24], were affected by the targeting strategy. [score:4]
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[+] score: 3
Several miRNAs were found with different expression levels in PD mo dels, such as miR-135a-5p, -214 and -124 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mice [55– 58], miR-155 in AAV-α-Syn PD mice [59], and miR-10a, -10b, -212, -132, -495 in A30P tg mice [26]. [score:3]
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50
[+] score: 3
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-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-23b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-101a, mmu-mir-124-3, mmu-mir-125a, mmu-mir-130a, mmu-mir-9-2, mmu-mir-136, mmu-mir-138-2, mmu-mir-140, mmu-mir-144, mmu-mir-145a, mmu-mir-146a, mmu-mir-149, mmu-mir-152, mmu-mir-10b, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-185, mmu-mir-24-1, mmu-mir-191, mmu-mir-193a, mmu-mir-195a, mmu-mir-200b, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-204, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-130a, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-136, hsa-mir-138-1, hsa-mir-146a, hsa-mir-149, hsa-mir-185, hsa-mir-193a, hsa-mir-195, hsa-mir-320a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, mmu-mir-330, mmu-mir-339, mmu-mir-340, mmu-mir-135b, mmu-mir-101b, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-107, mmu-mir-10a, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-320, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-361, mmu-mir-361, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-340, hsa-mir-330, hsa-mir-135b, hsa-mir-339, hsa-mir-335, mmu-mir-335, mmu-mir-181b-2, mmu-mir-376b, mmu-mir-434, mmu-mir-467a-1, hsa-mir-376b, hsa-mir-485, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, mmu-mir-485, mmu-mir-541, hsa-mir-376a-2, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, mmu-mir-301b, mmu-mir-674, mmu-mir-146b, mmu-mir-467b, mmu-mir-669c, mmu-mir-708, mmu-mir-676, mmu-mir-181d, mmu-mir-193b, mmu-mir-467c, mmu-mir-467d, hsa-mir-541, hsa-mir-708, hsa-mir-301b, mmu-mir-467e, mmu-mir-467f, mmu-mir-467g, mmu-mir-467h, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, mmu-mir-467a-2, mmu-mir-467a-3, mmu-mir-467a-4, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-467a-9, mmu-mir-467a-10, hsa-mir-320e, hsa-mir-676, mmu-mir-101c, mmu-mir-195b, mmu-mir-145b, mmu-let-7j, mmu-mir-130c, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
The miRNA families that change expression in both mouse and human were: let-7, miR-7, miR-15, miR-101, miR-140, miR-152 (all validated by qPCR, P < 0.05), as well as miR-17, miR-34, miR-135, miR-144, miR-146, miR-301, miR-339, miR-368 (qPCR not performed). [score:3]
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[+] score: 3
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-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-21, hsa-mir-23a, hsa-mir-30a, hsa-mir-98, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-30a, mmu-mir-30b, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-132, mmu-mir-133a-1, mmu-mir-150, mmu-mir-155, mmu-mir-204, mmu-mir-205, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-217, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-150, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-34a, mmu-mir-98, mmu-mir-322, mmu-mir-338, hsa-mir-155, mmu-mir-17, mmu-mir-19a, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, mmu-mir-217, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-338, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, hsa-mir-18b, hsa-mir-503, mmu-mir-541, mmu-mir-503, mmu-mir-744, mmu-mir-18b, hsa-mir-541, hsa-mir-744, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
A previous study showed that runx2 is a target of miR-30c, miR-135a, miR-204, miR-133a, miR-217, miR-205, miR-34, miR-23a and miR-338 [34]. [score:3]
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Liu C. G. Wang J. L. Li L. Xue L. X. Zhang Y. Q. Wang P. C. MicroRNA-135a and -200b, potential Biomarkers for Alzheimer’s disease, regulate β secretase and amyloid precursor protein Brain Res. [score:3]
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Other miRNAs from this paper: mmu-mir-132, mmu-mir-135b, mmu-mir-135a-2
The protein Gmps that was found deregulated in all analysis is shown with protein name, fold-changes, and protein variability using global proteomics approach (B); HT22 cells and hippocampus: n = 4 and cortex: n = 5. Figure S5, Visualisation of the fold changes of snoRNA135 and ΔCt values between miRNA-135 and snoRNA135 in control and irradiated cells and tissues. [score:2]
The columns represent the fold changes of snoRNA135 in miRNA normalisation (A, C, E) and ΔCt values of the differences between the Ct values of miRNA-135 and snoRNA135 (B, D, and F) with standard errors of the mean (SEM) in vitro (HT22 cells: n = 4 for 4 hours and 24 hours post-irradiation) and in vivo (hippocampus [H]: n = 3 for 24 hours post-irradiation; cortex [C]: n = 3 for 24 hours post-irradiation) experimental set-ups. [score:1]
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Furthermore, miR-135 and miR-203 reduce tumor growth and metastasis of MD-MB-231 cells to the bones by targeting the runt-related transcription factor 2 (Runx2) [8]. [score:3]
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But only 13 miRNAs had significantly differential expression, they were let-7e, miR-30b, miR-30c, miR-34a, miR-96, miR-129-3p, miR-132, miR-134, miR-135a, miR-143, miR-146a, mkiR-154 and miR-183, respectively (Fig. 1C). [score:3]
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In addition, miR-340 and miR-135 were also the potential miRNAs that can repress Myc expression. [score:3]
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In addition, miR-335 was found to play an important role in oocyte meiotic maturation 42 and miR-135A regulates early embryonic development 43. [score:3]
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Currently, there are also few reports available regarding the miRNAs labeled with asterisks, such as miR–miR-135a* and miR–miR-29b*, and their functions are unclear possibly due to their low expression. [score:3]
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Zhu et al. has recently demonstrated that increased expression of miR-135a, protects diabetic mice against ischemia/reperfusion injury [58]. [score:3]
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For example, we found that the expression of 3 miRNA (mmu-miR-130b-3p, mmu-miR-135a-5p, mmu-miR-692) displayed no differences between tumor and parenchyma in the absence of cigarette smoke exposure and therefore their interaction statistics reflected exclusively the effects of exposure. [score:3]
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Linc-MD1 is required for appropriate muscle differentiation, at least in part because it regulates the levels of myocyte enhancer factor 2C (MEF2C) and mastermind-like protein 1 (MAML1) by sponging endogenous miR-133 and miR-135 in the cytoplasm of muscle cells [24]. [score:2]
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Of note, several miRNAs reported to regulate Runx1 and/or Runx2, such as miR-135a [50] and miR-203 [33], and are associated with invasive and metastatic PCa trend downwards but do not achieve significant differences between transgenic and non-transgenic animals. [score:2]
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H8255 [12] Brain tumor Rhbg Brainmir-196b a * 403_0_8 [17] myeloid Hoxa7/Hoxa9 BM* M15-5S8 [10] B cell* M35-5B3 [10] B cell* M17-5B5-1 [10] B cell* 45f23 [17] myeloid* 443_0_8 [17] myeloid* SL024-1 [18] myeloid* 143_1 [17] T cell* M35-5S2-1 [10] B cell* M8-5S2-1 [10] B cell mir-135a-1Dkm4.24 [15] B cell Wdr82 N/D Lung, breast cancer let-7gDkm83.2 [15] B cell Wdr82 Thymus mir-363* 0249. [score:1]
The exception, mir-135a-1, is located in the 3′ UTR of the gene 6230410P16Rik. [score:1]
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Higher or lower levels of miR-135 can alter anxiety- and depression-like behaviors in mice via regulating activity of serotonergic (5HT) neurons, 5HT levels in blood and brain, and behavioral response to antidepressant treatment [45]. [score:2]
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Fourth, our recent data further confirmed that miR-34c and miR-135a are involved in first cleavage in mouse zygotes [12], [13]. [score:1]
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S7 7. Nrf2 -dependent effect of 5 mg / kg PQ Nrf2(+/+) PQ5—Nrf2(–/–) PQ5 miR-135a, miR-376c, miR-31, miR-let-7i*, miR-669b*, miR-344, miR-15b, miR-700*, miR-3099, miR-377, miR-338-5p, miR-382, miR-219-3p and miR-310a S8 8. Nrf2 -dependent effect of 10 mg / kg PQ Nrf2(+/+) PQ10—Nrf2(–/–) PQ10 miR-495*, miR-154*, miR-let-7b, miR-1983, miR-103 and miR-26a S9 The miR-380-3p / Sp3 mRNA pathway is worth to mention here. [score:1]
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Plasma miR-22, miR-101b, miR-122, miR -133a, miR135a*, miR-192, miR193 and miR486 have been shown to be affected by liver damage [39]. [score:1]
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The reaction mixtures were incubated at 16 °C for 30 min, 42 °C for 30 min, 85 °C for 5 min, and 4 °C for 30 s. The values were normalized for housekeeping miR135. [score:1]
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miR-191 and miR-135 are required for long-lasting spine remo delling associated with synaptic long-term depression. [score:1]
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The age -dependent miRNAs, included in the consensus modules, have been reported to be related to aging or specifically to cardiac aging based on recent studies: miR-34a [8], miR-466d-3p [6], miR-152 [30] and miR-135a [34]. [score:1]
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These miRNAs include miR-135, miR-143/145, miR-189, and miR-204. [score:1]
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Such a scenario is supported by the fact that some non-coding RNAs have been shown to bind to miRNAs at functional level as demonstrated by an interaction of linc-MD1 with miR-133 and miR-135 [32]. [score:1]
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Other miRNAs from this paper: hsa-let-7f-1, hsa-let-7f-2, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-32, mmu-mir-1a-1, mmu-mir-133a-1, mmu-mir-134, mmu-mir-144, mmu-mir-181a-2, mmu-mir-24-1, mmu-mir-200b, mmu-mir-206, hsa-mir-208a, mmu-mir-122, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, hsa-mir-214, hsa-mir-200b, mmu-mir-299a, mmu-mir-302a, hsa-mir-1-2, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-144, hsa-mir-134, hsa-mir-206, mmu-mir-200a, mmu-mir-208a, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-24-2, mmu-mir-328, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-214, mmu-mir-135a-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-200a, hsa-mir-302a, hsa-mir-299, hsa-mir-361, mmu-mir-361, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-377, mmu-mir-377, hsa-mir-328, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, hsa-mir-20b, hsa-mir-429, mmu-mir-429, hsa-mir-483, hsa-mir-486-1, hsa-mir-181d, mmu-mir-483, mmu-mir-486a, mmu-mir-367, mmu-mir-20b, hsa-mir-568, hsa-mir-656, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, mmu-mir-744, mmu-mir-181d, mmu-mir-568, hsa-mir-892a, hsa-mir-892b, mmu-mir-208b, hsa-mir-744, hsa-mir-208b, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-1307, eca-mir-208a, eca-mir-208b, eca-mir-200a, eca-mir-200b, eca-mir-302a, eca-mir-302b, eca-mir-302c, eca-mir-302d, eca-mir-367, eca-mir-429, eca-mir-328, eca-mir-214, eca-mir-200c, eca-mir-24-1, eca-mir-1-1, eca-mir-122, eca-mir-133a, eca-mir-144, eca-mir-25, eca-mir-135a, eca-mir-568, eca-mir-133b, eca-mir-206-2, eca-mir-1-2, eca-let-7f, eca-mir-24-2, eca-mir-134, eca-mir-299, eca-mir-377, eca-mir-656, eca-mir-181a, eca-mir-181b, eca-mir-32, eca-mir-486, eca-mir-181a-2, eca-mir-20b, eca-mir-361, mmu-mir-486b, mmu-mir-299b, hsa-mir-892c, hsa-mir-486-2, eca-mir-9021, eca-mir-1307, eca-mir-744, eca-mir-483, eca-mir-1379, eca-mir-7177b, eca-mir-8908j
From the 31 liver-specific miRNAs reported by Kim et al. [9], only one was supported by our study with our definition of tissue specificity (eca-miR-135a). [score:1]
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