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20 publications mentioning mmu-mir-504

Open access articles that are associated with the species Mus musculus and mention the gene name mir-504. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 329
To identify the putative miR-7, miR-34a, and miR-504 targets in the Shank3 interactome, we first pooled all the putative targets for each miRNA from six different prediction tools (TargetScan [http://targetscan. [score:9]
It is tempting to speculate that increased expression of miR-504 in the prefrontal cortex of bipolar disorder [32] might contribute to pathogenesis, at least partly, by downregulating SHANK3 expression and dendritic spines as we demonstrated in the cultured hippocampal neurons. [score:8]
miR-7, miR-34a, and miR-504 directly regulate the expression of SHANK3Using the TargetScan prediction tool (Release 6.2, http://www. [score:7]
To understand whether Shank3 expression was required for the spine changes observed after miR-7 or miR-504 inhibition, we co -transfected a previously validated siRNA targeting mouse Shank3 [12]. [score:7]
Together, these results suggest that miR-7, miR-34a, and miR-504 directly bind to the SHANK3 3′UTR and downregulate its expression. [score:7]
We found that miR-7, miR-34a, and miR-504, three miRNAs with altered expression profiles in multiple neuropsychiatric disorders, directly regulate SHANK3 expression. [score:7]
As miR-7, miR-34a, and miR-504 are expressed in mouse hippocampal neurons [39– 41], we decided to test the effect of inhibition of endogenous miRNAs on SHANK3 expression and dendritic spines. [score:7]
Transfection of locked-nucleic acid (LNA) inhibitors against each of the miRNAs increased the luciferase activity of wild-type, but not the respective binding site-mutant, SHANK3 3′UTR constructs, suggesting that endogenous miR-7, miR-34a, and miR-504 could regulate SHANK3 expression (Fig.   3f and g). [score:6]
In addition to SHANK3, miR-504 also regulates the expression of the dopamine D1 receptor gene (DRD1) [56], expression or activity of which is associated with multiple neuropsychiatric disorders including mood disorders [57]. [score:6]
Furthermore, the expression of rat Shank3 3′UTR, where the second miR-7 binding site of human 3′UTR is not conserved, was still reduced by miR-7 in the luciferase assay (Fig.   1b), indicating that the first site in the SHANK3 3′UTR is the only functional target site for miR-7. Expression of miR-34a or miR-504 also decreased the luciferase activity of the wild-type SHANK3 3′UTR construct in HEK293T cells (Fig.   1c and d). [score:6]
Together, our results provide new insight into the miRNA -mediated regulation of SHANK3 expression, and its potential implications for multiple neuropsychiatric disorders with altered expression profiles of miR-7, miR-34a, and miR-504. [score:6]
miR-7, miR-34a, and miR-504 directly regulate the expression of SHANK3. [score:5]
d Representative western blot images show that overexpression of miR-7 or miR-504 decreased the expression of the rat Shank3 construct with the 3′UTR, but not of that without the 3′UTR, in HEK293T cells. [score:5]
These results suggest that miR-7, miR-34a, and miR-504 could also potentially regulate the expression of some Shank3-interacting proteins, especially those involved in actin regulation. [score:5]
Moreover, opposite to the miRNA overexpression, miR-7 or miR-504 inhibition increased spine density in cultured mouse hippocampal neurons (Fig.   3h). [score:5]
Taken together, these results suggest that miR-7, miR-34a, and miR-504 could regulate SHANK3 expression in cultured mouse hippocampal neurons, and that miR-7 and miR-504 could regulate dendritic spines in a Shank3 -dependent manner. [score:5]
Fig. 4Lentiviral overexpression of miR-504 in cultured neurons, and expression analysis of miR-504 in human and mouse brain. [score:5]
Nevertheless, after normalization with EGFP, the expression of Shank3 with 3′UTR, but not that without 3′UTR, was significantly decreased by miR-7. e Co-transfection of the Shank3 construct without the 3′UTR, but not that with the 3′UTR, rescued the decreased dendritic spine density by miR-7 or miR-504 overexpression (n = 20–30). [score:5]
Lentivirus -mediated overexpression of miR-504, which mimics its reported expression change in postmortem brain tissues of bipolar disorder, decreased endogenous Shank3 protein in cultured hippocampal neurons. [score:5]
When we picked those targets suggested by more than two prediction tools, 79, 67, and 46 genes in the Shank3 interactome were revealed as putative targets for miR-7, miR-34a, and miR-504, respectively (Fig.   2a). [score:5]
g LNA -inhibitor against miR-7, miR-34a, and miR-504 did not affect the expression of the mutant SHANK3 3′UTR in cultured neurons. [score:5]
f LNA -inhibitor against miR-7, miR-34a, or miR-504 increased the expression of co -transfected SHANK3 3′UTR in cultured mouse hippocampal neurons. [score:5]
a Summary of the process identifying putative miR-7, miR-34a, and miR-504 targets in the Shank3 interactome (top), and the GO analysis of the putative targets (bottom). [score:5]
Moreover, overexpression or inhibition of miR-7 and miR-504 affected the dendritic spines of the cultured hippocampal neurons in a Shank3 -dependent manner. [score:5]
miR-7, miR-34a, and miR-504 potentially regulate other targets in the Shank3 interactome. [score:4]
Together, these results suggest that miR-7, miR-34a, and miR-504 could commonly regulate the expression of at least six major Shank3 isoforms (a, a[E10-12S V], c, d, e, and f) (Additional file 1: Figure S3) [8, 49]. [score:4]
In this study, we examine this possibility for the SHANK3 gene and report post-transcriptional regulation of SHANK3 expression by three miRNAs, miR-7, miR-34a, and miR-504, which were previously shown to be altered in some neuropsychiatric disorders that could also be caused by SHANK3 dosage changes. [score:4]
We further mutated the putative miRNA binding sites in the 3′UTRs of PFN2 and SPTBN2, the two genes most downregulated by miR-7 and miR-504, respectively, and found that the mutations abolished the effect of the miRNAs in the luciferase assays (Fig.   2d and e). [score:4]
In this study, we showed post-transcriptional regulation of SHANK3 expression in neurons by three miRNAs, miR-7, miR-34a, and miR-504. [score:4]
To directly visualize miR-504 expression, we next performed in situ hybridization of miR-504 in the brains of 3- and 8-week-old mice. [score:4]
We first pooled the putative human target genes for each of the three miRNAs from six prediction tools (total 8,246 targets for miR-7, 4,635 for miR-34a, and 3,392 for miR-504), and then compared these lists with 338 Shank3 interactome genes [12]. [score:4]
Here we show post-transcriptional regulation of SHANK3 expression by three microRNAs (miRNAs), miR-7, miR-34a, and miR-504. [score:4]
These results suggest that miR-504 might be an important regulator of gene expression in some cortical and limbic regions associated with mood disorders, an idea that is also partly supported by our results for the human and mouse brain distribution of miR-504. [score:4]
d Mutation of the second miR-504 binding site (M2) blocked its repressive effect on the expression of the SHANK3 3′UTR. [score:4]
e Mutation of the miR-504 binding site blocked its repressive effect on the expression of the human SPTBN2 3′UTR. [score:4]
Importantly, these dendritic spine changes were dependent on Shank3, suggesting that Shank3 functions as a core protein among the actin-related miR-7 and miR-504 targets in regulating dendritic spines. [score:4]
Altered expression profiles of miR-7, miR-34a, and miR-504 in multiple neuropsychiatric disorders. [score:3]
The number in parentheses associated with each brain region is the expression rank of miR-504 among all the 1,883 miRNAs available for the brain region. [score:3]
i Co-transfection of Shank3 siRNA blocked the increase of dendritic spines in response to miR-7 or miR-504 inhibition (n = 16–20). [score:3]
In the case of miR-504 inhibition, the density of the filopodia was decreased (Fig.   3h). [score:3]
To obtain the expression rank of miR-504 among all the 1,883 miRNAs for each brain region, the median value of each miRNA across all the samples in the brain region was computed, and the resulting median values of all miRNAs were ranked in descending order. [score:3]
Notably, expression of miR-504 was shown to be increased in the dorsolateral prefrontal cortex from postmortem brains of bipolar disorder [32], and in the nucleus accumbens in a rat mo del of depression induced by maternal deprivation followed by chronic unpredictable stress [44]. [score:3]
Statistical analyses are in 1: Table S3The validated target sites for miR-7, miR-34a, and miR-504 were highly conserved across different species (Fig.   1e). [score:3]
We transfected enhanced green fluorescent protein (EGFP) -expressing plasmid with control miRNA, miR-7, or miR-504 into cultured mouse hippocampal neurons, and immunostained the neurons with GFP antibody to visualize dendritic protrusions. [score:3]
We used a lentivirus expressing TurboGFP together with control miRNA or miR-504. [score:3]
The expression of Shank3 construct with 3′UTR, but not that without 3′UTR, was significantly decreased by miR-7 and miR-504 in mouse cultured neurons. [score:3]
b Representative western blot images and quantification showing that lentiviral overexpression of miR-504 decreased endogenous Shank3, but not Shank2 and PSD-95, proteins in cultured hippocampal neurons. [score:3]
We found that both miR-7 and miR-504 overexpression decreased dendritic spine density, but neither of the miRNAs affected filopodia (Fig.   3c). [score:3]
TargetScan predicted that the SHANK2 3′UTR contained conserved miR-7, but not miR-34a or miR-504, binding sites. [score:3]
These reports, together with our results from spine analysis, prompted us to test the effect of miR-504 overexpression on endogenous Shank3 levels. [score:3]
Human and mouse brain expression patterns of miR-504. [score:3]
The expression of miR-7, miR-34a and miR-504 were reported to be altered in the postmortem brains, fibroblasts, or blood samples of patients with schizophrenia, depression, or bipolar disorder (Additional file 1: Table S2) [29– 34]. [score:3]
a miR-7, miR-34a, or miR-504 overexpression decreased the luciferase activity of wild-type SHANK3 3′UTR in cultured mouse hippocampal neurons. [score:3]
However, only the Shank3 construct without the 3′UTR could rescue the decreased spine density in response to miR-7 or miR-504 overexpression (Fig.   3e). [score:3]
Statistical analyses are in 1: Table S3 The validated target sites for miR-7, miR-34a, and miR-504 were highly conserved across different species (Fig.   1e). [score:3]
Indeed, in HEK293T cells, miR-7 and miR-504 reduced the expression of Shank3 proteins from the construct with the 3′UTR, but did not affect the construct without the 3′UTR (Fig.   3d). [score:3]
a Representative images of live neurons infected with lentivirus expressing TurboGFP together with miR-504. [score:3]
To explore the regional expression pattern of miR-504, the dataset was divided into 16 brain regions, with the samples from the same brain region being grouped together. [score:3]
The expression of other synaptic proteins, Shank2 and PSD-95, were not significantly changed by miR-504 (Fig.   4b). [score:3]
Similar to the expression pattern in human brains, strong miR-504 signals were detected in the cortex and hippocampus from both stages (Fig.   4d). [score:3]
Additional luciferase assays using the SHANK3 3′UTR constructs with single or multiple mutations in the putative binding sites revealed that each miRNA had a single functional target site in the SHANK3 3′UTR (549–556 for miR-34a, and 1, 713-1, 720 for miR-504) (Fig.   1c and d). [score:3]
We also revealed that miR-504 is expressed in the cortical and hippocampal regions of human and mouse brains. [score:3]
c Box plots showing the expression distribution of miR-504 in 16 human brain regions. [score:3]
Lentiviral particles expressing TurboGFP together with the mature form of a control miR (Dharmacon, S05-005000-01) or miR-504 (shMIMIC Dharmacon, VSM6213-213638367) under a CAG promoter were applied to cultured hippocampal neurons (DIV 1, multiplicity of infection of 5) prepared from embryonic day 18 rats. [score:3]
Together, these results suggest that the increased expression of miR-504 observed in postmortem brains of bipolar disorder and in a rat mo del of depression, might possibly lead to a decrease in Shank3 protein in some brain regions. [score:3]
In terms of the expression rank of miR-504 among all the 1,883 miRNAs available for each brain region, the primary somatosensory cortex (S1C) and cerebellar cortex showed the highest and lowest values, respectively (Fig.   4c). [score:3]
g miR-7, miR-34a, and miR-504 synergistically decreased the expression of the SHANK3 3′UTR. [score:3]
c Overexpression of miR-7 or miR-504 decreased the density of dendritic spines in cultured mouse hippocampal neurons (n = 16–30). [score:3]
Moreover, maternal deprivation followed by chronic unpredictable stress increases miR-504 expression in the rat nucleus accumbens where the miR-504 levels are positively correlated with the severity of depression-like behavior after stress [44]. [score:3]
When expressed at a fixed total amount, miR-7, miR-34a, and miR-504 in combination decreased the luciferase activity of SHANK3 3′UTR more efficiently than each miRNA alone, suggesting their synergistic effect (Fig.   1g). [score:3]
h LNA -inhibitor against miR-7 or miR-504 increased dendritic spines in cultured neurons (n = 18–20). [score:3]
We decided to further characterize miR-504, as it most significantly downregulated SHANK3 levels and changed dendritic spines among the three miRNAs we tested (Figs.   1 and 3). [score:2]
Therefore, we searched for proteins in the Shank3 interactome that might also be regulated by miR-7, miR-34a, or miR-504. [score:2]
Consistent with our results from the luciferase assays, infection of the virus expressing miR-504 decreased Shank3 proteins in cultured hippocampal neurons confirmed by western blot experiments (Fig.   4a and b). [score:2]
miR-7 and miR-504 regulate dendritic spines of cultured hippocampal neurons. [score:2]
c miR-7, miR-34a, and miR-504 decreased the expression of the 3′UTRs of some Shank3-interacting proteins in luciferase assays. [score:2]
Fig. 2Regulation of Shank3-interacting actin-related proteins by miR-7, miR-34a, and miR-504. [score:2]
We found that Shank3 siRNA alone resulted in lower spine density compared to that observed with control siRNA, and that it also blocked the increase in spine density in response to miR-7 or miR-504 inhibition (Fig.   3i). [score:2]
Fig. 3miR-7 and miR-504 regulate dendritic spines of cultured hippocampal neurons in a Shank3 -dependent manner. [score:2]
These lists (8,246 targets for miR-7, 4,635 for miR-34a, and 3,392 for miR-504) were compared with the 388 proteins in the Shank3 interactome. [score:2]
After washing with PBS, the brain sections were incubated in hybridization buffer for 2 h at 60 °C, followed by overnight hybridization with 60 ng/ml DIG-labeled riboprobe against miR-504 (Exiqon, 38654-15) at 60 °C. [score:1]
Consistent with the results from HEK293T cells (Fig.   1), miR-7, miR-34a, and miR-504 decreased the luciferase activity of the wild-type, but not the respective binding site-mutant, SHANK3 3′UTR constructs (Fig.   3a and b). [score:1]
Finally, we chose three miRNAs, miR-7, miR-34a, and miR-504 because of their strong 8-mer type binding sites [20] in the SHANK3 3′UTR. [score:1]
We further characterized miR-504 as it showed the most significant effect on both SHANK3 expression and dendritic spines among the three miRNAs. [score:1]
We found that miR-504 was detected throughout all brain regions, with the highest median value of reads per million mapped reads (RPM) found in the hippocampus (HIP), and the lowest median value found in the cerebellar cortex (CBC) (Fig.   4c). [score:1]
Generation and behavioral characterization of animal mo dels with altered miR-504 expression in these brain regions could help us test this intriguing hypothesis. [score:1]
Statistical analyses are in 1: Table S3 Although miR-504 was detected in some brain regions including the cortex [32], hippocampus [41], and nucleus accumbens [44], its overall expression pattern in the brain has not been characterized. [score:1]
To understand this, we first investigated the regional expression pattern of miR-504 in human brain by performing bioinformatic analyses on the developing human brain miRNA sequencing data from the BrainSpan database (http://www. [score:1]
Consistently, both gain- and loss-of-function experiments showed that miR-7 and miR-504 control actin-rich dendritic spines. [score:1]
To understand the human brain distribution of miR-504, the miRNA sequencing data of the developing human brain were downloaded from the BrainSpan database (http://www. [score:1]
miR-504 signals were detected in neurons of cortex and hippocampus, and in Purkinje cells of cerebellum from 3- and 8-week-old mice. [score:1]
We transfected cultured hippocampal neurons with control miRNA, miR-7, or miR-504 in combination with the two Shank3 constructs. [score:1]
Consistently, the expression of Shank3 construct with 3′UTR, but not that without 3′UTR, was decreased by miR-7 and miR-504 in cultured neurons measured by immunostaining (Additional file 1: Figure S2). [score:1]
d In situ hybridization of miR-504 in mouse brains. [score:1]
b miR-7, miR-34a, and miR-504 did not affect the luciferase activity of the mutant SHANK3 3′UTR constructs in cultured neurons. [score:1]
Statistical analyses are in 1: Table S3Although miR-504 was detected in some brain regions including the cortex [32], hippocampus [41], and nucleus accumbens [44], its overall expression pattern in the brain has not been characterized. [score:1]
h miR-7, miR-34a, and miR-504 did not affect the mRNA levels of the SHANK3 3′UTR. [score:1]
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2
[+] score: 133
Importantly, the growth suppression was associated with increased p53 protein expression and down-regulation of miR-504. [score:8]
The miR-504 has been reported as a negative regulator of p53 through its direct binding in the p53 3' untranslated region, thereby decreasing p53 function and protein expression, without affecting mRNA levels [28]. [score:7]
We have demonstrated that the TFF1 activation of p53 involves down-regulation of miR-504 expression, a negative regulator of p53. [score:7]
The reconstitution of TFF1 expression significantly reduced miR-504 expression, but not miR-125, in AGS (A) and STKM2 (B) cells; the levels of TFF1 mRNA expression are shown. [score:7]
In this study, we identified a novel mechanism by which TFF1 suppresses cell growth and induces apoptosis through activation of p53, by down-regulation of miR-504, a negative regulator of p53, in gastric cancer cells. [score:7]
TFF1 activates p53 through down-regulation of miR504 expression. [score:6]
In fact, our data demonstrated that the reconstitution of TFF1 expression significantly down-regulated endogenous miR-504, which led to increased p53 protein levels in gastric cancer cells. [score:6]
These results confirmed that TFF1 inhibits gastric tumor growth through activation of p53 and down-regulation of miR-504 in vivo. [score:6]
We postulated that TFF1 could activate p53 through down-regulation of miR-504 expression. [score:6]
To test this hypothesis, we first checked the microRNA expression of miR-125 and miR-504 in response to TFF1 expression. [score:5]
Together, our data indicated that TFF1 induces p53 activation through down-regulation of miR-504, a negative regulator of p53, in gastric cancer cells. [score:5]
Hence, overexpression of miR-504 inhibits the transcriptional activity of p53 and decreases the p53 -induced apoptosis and cell-cycle arrest in response to genotoxic stress, suggesting that miR-504 may be implicated in tumorigenesis. [score:5]
Overexpression of miR-504 reduced TFF1 -induced p53 protein expression in AGS (C) and STKM2 (D) cells. [score:5]
Quantitative real time PCR data showed that TFF1 xenografts displayed a significantly less expression of miR-504 expression than control xenografts (p<0.05, Figure 6F). [score:5]
To confirm the role of miR-504 in suppressing p53 induction in a different mo del, we transiently transfected AGS cells with control empty vector or miR-504 expression vector and treated with vehicle or CDDP (10 μM) for 6 hours. [score:5]
Hu and colleagues [28] identified a novel miRNA, miR-504, which acts as a negative regulator of p53 expression through its binding to two sites in p53 3′-UTR. [score:4]
TFF1 activates p53 through down-regulation of miR-504. [score:4]
We have shown the effects of TFF1 on preventing tumor growth and promoting apoptosis by regulating the tumor suppressor gene p53 through miR-504. [score:4]
Furthermore, we confirmed that overexpression of exogenous miR-504 significantly abrogated TFF1 -induced activation of p53, indicating that miR-504 mediates the effect of TFF1. [score:3]
The quantitative real time PCR data showed that the reconstitution of TFF1 expression significantly decreased miR-504 levels, but not miR-125, in AGS (p<0.05, Figure 4A) and STKM2 (p<0.01, Figure 4B) cells, suggesting that. [score:3]
The Western blot analysis data showed that the reconstitution of miR-504 suppressed CDDP -induced p53 protein level in AGS (Figure 4E) and STKM2 (Figure 4F) cells. [score:3]
To validate the role of miR-504 in the induction of p53 by TFF1, we transiently transfected AGS and STKM2 cells with TFF1 or PTT5 empty vector in combination with control empty vector or miR-504 expression vector, and subjected to Western blot analysis. [score:3]
AGS and STKM2 cells were transiently transfected with PTT5 empty vector or TFF1 in combination with control empty vector or miR-504 expression vector, and subjected to Western blot analysis. [score:3]
Recent studies showed that some microRNAs, such as miR-504 and miR-125, may directly regulate p53 by reducing its protein levels [28, 34, 35]. [score:3]
Human pre-microRNA Expression Construct Lenti-miR-504 from System Biosciences (Mountain View, CA). [score:3]
However, since TFF1 is a secreted protein [44], the precise mechanism by which TFF1 regulates miR-504 expression to activate p53 requires further investigation. [score:2]
Protein levels and function of p53 have been shown to be regulated by miRNAs including miR-125 [43], miR-18 [23], and miR-504 [28]. [score:2]
The miRNA levels of endogenous mature miR-125 and miR-504 were analyzed and normalized with miR-191. [score:1]
AGS and STKM2 cells were transiently transfected with control empty vector or miR-504 plasmid for 48 h, treated with CDDP for 6 h, and subjected to Western blot analysis of p53. [score:1]
Our data indicated that the reconstitution of miR-504 significantly decreased TFF1 -induced p53 protein levels in AGS (Figure 4C) and STKM2 (Figure 4D) cells. [score:1]
The reconstitution of miR-504 reduced CDDP -induced p53 protein levels in AGS (E) and STKM2 (F) cells. [score:1]
AGS and STKM2 cells were transiently transfected with PTT5 empty vector or TFF1 and subjected to quantitative real-time PCR of mature miR-125, miR-504, and TFF1 48 hours post transfection. [score:1]
Figure 4 AGS and STKM2 cells were transiently transfected with PTT5 empty vector or TFF1 and subjected to quantitative real-time PCR of mature miR-125, miR-504, and TFF1 48 hours post transfection. [score:1]
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3
[+] score: 61
Other miRNAs from this paper: mmu-mir-125a, mmu-mir-125b-2, mmu-mir-125b-1
Using Wnt-1 p53 [+/+] and Wnt-1 p53 [+/−] mouse mo dels of postmenopausal basal-like breast cancer, we provide evidence that a DIO regimen (relative to control diet and regardless of tumoral p53 genotype): i) promotes mammary tumor progression, more severe tumor pathology, EMT, and loss of ERα protein expression; and ii) suppresses tumoral p53 and p21 protein expression in association with increased expression of the negative regulator of p53, miR-504. [score:10]
However, tumoral miR-504 and p53 levels were inversely associated, suggesting that the observed DIO upregulation of miR-504 expression contributes to the reduced p53 protein (but not mRNA) expression. [score:8]
However, the effect of obesity on miR-125b and miR-504, which negatively regulate p53 through direct binding in the 3′ untranslated region of the gene, resulting in decreased p53 protein translation (7,8), is unclear. [score:7]
Specifically, DIO, relative to control, increases mammary tumor progression, local tissue invasion, and EMT programming, and suppresses protein expression of p53, p21, and ERα, possibly through elevated miR-504 expression. [score:7]
In human glioblastomas, miR-504 expression correlates with the expression of several EMT- or stem cell-related markers [48]. [score:5]
DIO Suppressed p53 Signaling and Increased miR-504 Expression in Wnt-1 Mammary Tumors. [score:5]
Furthermore, miR-504, an obesity-responsive negative regulator of p53 (and hence p21 and ERα) and putative regulator of EMT, may represent a novel molecular target for breaking the obesity-breast cancer link. [score:5]
In contrast, DIO, relative to control, significantly increased expression of miR-504, also a negative regulator of p53, in Wnt-1 p53 [+/+] tumor tissue (P = 0.013) and Wnt-1 p53 [+/−] tumor tissue (P = 0.032, Figure 6). [score:4]
Expression of miR-504 in the tumor cell suspensions (same batch used for the tumor transplant study) was also significantly increased in the Wnt-1 p53 [+/−] cells compared with Wnt-1 p53 [+/+] cells (1.91+/−0.11 versus 1.05+/−0.12 relative expression units; P = 0.002). [score:4]
Negative regulators of p53 include the p53 acetylator Sirtuin 1 (SIRT1) [10], the ubiquitin ligase mouse double minute 2 (MDM2) [11], microRNA (miR)-125b [12] and miR-504 [13]. [score:2]
Another possible role of miR-504 in DIO -associated mammary tumor progression involves the putative interaction between miR-504, p53 and EMT. [score:1]
mRNA expression, measured by quantitative real-time PCR, of p53, mouse double minute (MDM2), Sirtuin (Sirt)1, microRNA (miR)-125b and miR-504 (n = 5 per gene per group; 3 replicates) in Wnt-1 p53 [+/+] and Wnt-1 p53 [+/−] tumor tissue from DIO or control mice. [score:1]
Future studies on the links between obesity-related hormones, miR504 and p53 are warranted. [score:1]
0068089.g006 Figure 6mRNA expression, measured by quantitative real-time PCR, of p53, mouse double minute (MDM2), Sirtuin (Sirt)1, microRNA (miR)-125b and miR-504 (n = 5 per gene per group; 3 replicates) in Wnt-1 p53 [+/+] and Wnt-1 p53 [+/−] tumor tissue from DIO or control mice. [score:1]
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4
[+] score: 23
miR-504-3p and miR-455-3p were downregulated at magnetic field intensities of 1 mT and 3 mT and upregulated in response to a 2 mT electromagnetic field (E and G). [score:7]
miR-504-3p and miR-455-3p were downregulated at magnetic field intensities of 1 mT and 3 mT, but upregulated in response to a 2 mT electromagnetic field. [score:7]
The expression levels of miR-26b-5p, miR-30e-5p, miR-210-5p, miR-224-5p, miR-196b-5p, miR-504-3p and miR-669c-5p significantly differed between the ELF-EMF and the sham groups (Fold change > 2.0). [score:3]
Following the network analysis and confirmation of the miRNA array data via real-time PCR, we examined the effect of the magnetic field intensity on the expression levels of miR-30e-5p, miR-210-5p, miR-224-5p, miR-196b-5p, miR-504-3p, miR-669c-5p and miR-455-3p (Fig 6). [score:3]
Among the selected miRNAs, the expression levels of miR-26b-5p, miR-30e-5p, miR-210-5p, miR-224-5p, miR-196b-5p, miR-504-3p and miR-669c-5p significantly changed compared with the sham group (Fold change > 2.0). [score:2]
However, miR-30e-5p, miR-210-5p, miR-224-5p, miR-196b-5p, miR-504-3p, miR-669c-5p and miR-455-3p may be closely related to the epigenetic mechanism associated with ELF-EMF exposure at a magnetic field intensity of 3 mT (Fig 5B). [score:1]
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5
[+] score: 15
Other miRNAs from this paper: mmu-mir-30a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-132, mmu-mir-134, mmu-mir-135a-1, mmu-mir-138-2, mmu-mir-142a, mmu-mir-150, mmu-mir-154, mmu-mir-182, mmu-mir-183, mmu-mir-24-1, mmu-mir-194-1, mmu-mir-200b, mmu-mir-122, mmu-mir-296, mmu-mir-21a, mmu-mir-27a, mmu-mir-92a-2, mmu-mir-96, rno-mir-322-1, mmu-mir-322, rno-mir-330, mmu-mir-330, rno-mir-339, mmu-mir-339, rno-mir-342, mmu-mir-342, rno-mir-135b, mmu-mir-135b, mmu-mir-19a, mmu-mir-100, mmu-mir-139, mmu-mir-212, mmu-mir-181a-1, mmu-mir-214, mmu-mir-224, mmu-mir-135a-2, mmu-mir-92a-1, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-125b-1, mmu-mir-194-2, mmu-mir-377, mmu-mir-383, mmu-mir-181b-2, rno-mir-19a, rno-mir-21, rno-mir-24-1, rno-mir-27a, rno-mir-30a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-96, rno-mir-100, rno-mir-101a, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-132, rno-mir-134, rno-mir-135a, rno-mir-138-2, rno-mir-138-1, rno-mir-139, rno-mir-142, rno-mir-150, rno-mir-154, rno-mir-181b-1, rno-mir-181b-2, rno-mir-183, rno-mir-194-1, rno-mir-194-2, rno-mir-200b, rno-mir-212, rno-mir-181a-1, rno-mir-214, rno-mir-296, mmu-mir-376b, mmu-mir-370, mmu-mir-433, rno-mir-433, mmu-mir-466a, rno-mir-383, rno-mir-224, mmu-mir-483, rno-mir-483, rno-mir-370, rno-mir-377, mmu-mir-542, rno-mir-542-1, mmu-mir-494, mmu-mir-20b, mmu-mir-503, rno-mir-494, rno-mir-376b, rno-mir-20b, rno-mir-503-1, mmu-mir-1224, mmu-mir-551b, mmu-mir-672, mmu-mir-455, mmu-mir-490, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-466d, mmu-mir-872, mmu-mir-877, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-872, rno-mir-877, rno-mir-182, rno-mir-455, rno-mir-672, mmu-mir-466l, mmu-mir-466i, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, rno-mir-551b, rno-mir-490, rno-mir-1224, rno-mir-504, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-466b-8, rno-mir-466d, mmu-mir-466q, mmu-mir-21b, mmu-mir-21c, mmu-mir-142b, mmu-mir-466c-3, rno-mir-322-2, rno-mir-503-2, rno-mir-466b-3, rno-mir-466b-4, rno-mir-542-2, rno-mir-542-3
DEX treatment up-regulated the expression of miRNA-483, miRNA-181a-1, miRNA-490 and miRNA-181b-1, while it down-regulated the levels of miR-122, miR-466b, miR-200b, miR-877, miR-296, miRNA-27a and precursor of miR-504. [score:9]
In contrast, dexamethasone down-regulated the expression of several of the miRNAs by more than 1.5 fold, i. e., miR-122 (8.2-fold), miR-466b (2.31-fold), miR-200b (1.9-fold) miR-877 (1.61-fold), miR-296 (1.61-fold)and precursor of miR-504 (1.53-fold) (Fig. 2D ). [score:6]
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6
[+] score: 10
B. qRT-PCRs showed that miR-382-5p was upregulated, while miR-504-3p, -3068-3p, -664-5p, and -5100 were downregulated in the mouse liver at PH-48h (n=5). [score:7]
As miR-504-3p was found to be downregulated in the mouse liver at PH-48h using qRT-PCR which was contrary to the result of microarrays (Figure 1A and 1B), miR-504-3p was then excluded for subsequent functional assays. [score:3]
[1 to 20 of 2 sentences]
7
[+] score: 7
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, mmu-mir-23b, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-127, mmu-mir-128-1, mmu-mir-132, mmu-mir-133a-1, mmu-mir-188, mmu-mir-194-1, mmu-mir-195a, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-205, mmu-mir-206, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-122, mmu-mir-30e, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-211, hsa-mir-212, hsa-mir-214, hsa-mir-217, hsa-mir-200b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-127, hsa-mir-138-1, hsa-mir-188, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, 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-7f-1, mmu-let-7f-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-31, mmu-mir-351, hsa-mir-200c, mmu-mir-17, mmu-mir-19a, mmu-mir-100, mmu-mir-200c, mmu-mir-212, mmu-mir-214, mmu-mir-26a-2, mmu-mir-211, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-19b-1, mmu-mir-138-1, mmu-mir-128-2, hsa-mir-128-2, mmu-mir-217, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-379, mmu-mir-379, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-412, mmu-mir-431, hsa-mir-431, hsa-mir-451a, mmu-mir-451a, mmu-mir-467a-1, hsa-mir-412, hsa-mir-485, hsa-mir-487a, hsa-mir-491, hsa-mir-503, hsa-mir-504, mmu-mir-485, hsa-mir-487b, mmu-mir-487b, mmu-mir-503, hsa-mir-556, hsa-mir-584, mmu-mir-665, mmu-mir-669a-1, mmu-mir-674, mmu-mir-690, mmu-mir-669a-2, mmu-mir-669a-3, mmu-mir-669c, mmu-mir-696, mmu-mir-491, hsa-mir-665, mmu-mir-467e, mmu-mir-669k, mmu-mir-669f, hsa-mir-664a, mmu-mir-1896, mmu-mir-1894, mmu-mir-1943, mmu-mir-1983, mmu-mir-1839, mmu-mir-3064, mmu-mir-3072, mmu-mir-467a-2, mmu-mir-669a-4, mmu-mir-669a-5, mmu-mir-467a-3, mmu-mir-669a-6, mmu-mir-467a-4, mmu-mir-669a-7, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-669a-8, mmu-mir-669a-9, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-669a-10, mmu-mir-467a-9, mmu-mir-669a-11, mmu-mir-467a-10, mmu-mir-669a-12, mmu-mir-3473a, hsa-mir-23c, hsa-mir-4436a, hsa-mir-4454, mmu-mir-3473b, hsa-mir-4681, hsa-mir-3064, hsa-mir-4436b-1, hsa-mir-4790, hsa-mir-4804, hsa-mir-548ap, mmu-mir-3473c, mmu-mir-5110, mmu-mir-3473d, mmu-mir-5128, hsa-mir-4436b-2, mmu-mir-195b, mmu-mir-133c, mmu-mir-30f, mmu-mir-3473e, hsa-mir-6825, hsa-mir-6888, mmu-mir-6967-1, mmu-mir-3473f, mmu-mir-3473g, mmu-mir-6967-2, mmu-mir-3473h
In the microarray data, 12 miRNAs were consistent in their change either with HHcy or diabetes; of which 4 miRNAs were downregulated in both groups (miR-16, miR-1983, miR-412 and miR-487) and 8 miRNAs (miR-194, miR-188, miR-1896, miR-467e, miR-504, miR-5110, miR-669k and miR-696) were upregulated in both groups. [score:7]
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8
[+] score: 7
The upregulated miRNAs included mmu-miR-34a-5p, mmu-miR-129b-5p, mmu-miR-451a, mmu-miR-144-5p and mmu-miR-129b-3p, whereas highly downregulated miRNAs included mmu-miR-100-5p, mmu-miR-99a-5p, mmu-miR-33-5p, mmu-miR-125a-5p, mmu-miR-128-1-5p, mmu-miR-181b-1-3p, mmu-miR-188-5p, mmu-miR-196b-5p, mmu-miR-211-5p, mmu-miR-224-5p, mmu-miR-455-3p, mmu-miR-504-5p, mmu-miR-592-5p, mmu-miR-5107-3p, mmu-miR-5120, and mmu-let-7i-3p. [score:7]
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9
[+] score: 6
For instance, miR-125b, miR-504 and miR-30 can target p53 and down-regulate p53 protein levels and function [24– 26]. [score:6]
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10
[+] score: 6
Hu W. Chan C. S. Wu R. Zhang C. Sun Y. Song J. S. Tang L. H. Levine A. J. Feng Z. Negative regulation of tumor suppressor p53 by microRNA miR-504 Mol. [score:4]
miR-504 was the first miRNA identified and validated by Hu et al. as a negative regulator of p53 [103]. [score:2]
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[+] score: 6
Deregulated miR expression profiles might also contribute to oncogenesis by repressing the tumor suppressors, p21/p53 (miR-25 [42], [43], miR-504 [44]) which in turn might affect Wnt signaling. [score:6]
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12
[+] score: 5
Other miRNAs from this paper: mmu-mir-142a, mmu-mir-294, mmu-mir-10a, mmu-mir-142b
One previous study showed that miR-504 specifically targets a polymorphic site in human D1 3′UTR that is associated with nicotine dependence; however in that study miR-504 was found to increase, rather than decrease, the expression level of the human D1 receptor mRNA [19]. [score:5]
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13
[+] score: 4
For instance, it has been observed that miR-125b [84] and miR-504 [85], when overexpressed, keep the p53 level low by direct binding to the p53 mRNA. [score:4]
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14
[+] score: 4
Several other miRNAs, such as miR-150, miR-504 and miR-322 have all been shown to regulate VEGFA expression (Figure 4). [score:4]
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15
[+] score: 4
Hu W. Chan C. S. Wu R. Zhang C. Sun Y. Song J. S. Tang L. H. Levine A. J. Feng Z. Negative regulation of tumor suppressor p53 by microRNA mir-504 Mol. [score:4]
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16
[+] score: 3
miR-504 reduces etoposide-caused apoptosis by targeting p53 [14]. [score:3]
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17
[+] score: 3
Figure 1 MicroRNAs targeting p53: miR-125b, miR-504, miR-1285, miR-92, miR-141, miR-380-5p, miR-15a, miR-16, miR-25, miR-30d, miR-200a [reviewed in Ref. [score:3]
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18
[+] 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-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-138-2, mmu-mir-181a-2, mmu-mir-182, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-181a-1, mmu-mir-297a-1, mmu-mir-297a-2, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-138-2, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-138-1, 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-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, rno-mir-301a, rno-let-7d, rno-mir-344a-1, mmu-mir-344-1, rno-mir-346, mmu-mir-346, rno-mir-352, hsa-mir-181b-2, mmu-mir-10a, mmu-mir-181a-1, mmu-mir-29b-2, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-125b-1, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-30e, hsa-mir-362, mmu-mir-362, hsa-mir-369, hsa-mir-374a, mmu-mir-181b-2, hsa-mir-346, 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-10a, rno-mir-15b, rno-mir-26b, 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-34b, rno-mir-34c, rno-mir-34a, rno-mir-106b, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-138-2, rno-mir-138-1, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-181a-1, hsa-mir-449a, mmu-mir-449a, rno-mir-449a, mmu-mir-463, mmu-mir-466a, hsa-mir-483, hsa-mir-493, hsa-mir-181d, hsa-mir-499a, hsa-mir-504, mmu-mir-483, rno-mir-483, mmu-mir-369, rno-mir-493, rno-mir-369, rno-mir-374, hsa-mir-579, hsa-mir-582, hsa-mir-615, hsa-mir-652, hsa-mir-449b, rno-mir-499, hsa-mir-767, hsa-mir-449c, hsa-mir-762, mmu-mir-301b, mmu-mir-374b, mmu-mir-762, mmu-mir-344d-3, mmu-mir-344d-1, mmu-mir-673, mmu-mir-344d-2, mmu-mir-449c, mmu-mir-692-1, mmu-mir-692-2, mmu-mir-669b, mmu-mir-499, mmu-mir-652, mmu-mir-615, mmu-mir-804, mmu-mir-181d, mmu-mir-879, mmu-mir-297a-3, mmu-mir-297a-4, mmu-mir-344-2, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-493, mmu-mir-466d, mmu-mir-449b, hsa-mir-374b, hsa-mir-301b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-879, mmu-mir-582, rno-mir-181d, rno-mir-182, rno-mir-301b, rno-mir-463, rno-mir-673, rno-mir-652, mmu-mir-466l, mmu-mir-669k, mmu-mir-466i, mmu-mir-669i, mmu-mir-669h, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, mmu-mir-1193, mmu-mir-767, rno-mir-362, rno-mir-504, rno-mir-582, rno-mir-615, mmu-mir-3080, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-344e, mmu-mir-344b, mmu-mir-344c, mmu-mir-344g, mmu-mir-344f, mmu-mir-374c, mmu-mir-466b-8, hsa-mir-466, hsa-mir-1193, rno-mir-449c, rno-mir-344b-2, rno-mir-466d, rno-mir-344a-2, rno-mir-1193, rno-mir-344b-1, hsa-mir-374c, hsa-mir-499b, mmu-mir-466q, mmu-mir-344h-1, mmu-mir-344h-2, mmu-mir-344i, rno-mir-344i, rno-mir-344g, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-692-3, rno-let-7g, rno-mir-15a, rno-mir-762, mmu-mir-466c-3, rno-mir-29c-2, rno-mir-29b-3, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
1Proliferation, Invasion, Tumor suppression [63– 66] miR-344 ↓2.0 ↓3.2 NA miR-346 ↓2.4Proliferation [67, 68] miR-362 ↓2.3Proliferation, Invasion, Apoptosis [69– 76] miR-369 ↓2.8 ↓2.6 ↓2.1Aerobic glycolysis [77] miR-374 ↑3.0 ↓2.2 NA miR-449 ↑2.7 ↑2.4Proliferation [78– 81] miR-463 ↓2.7 NAmiR-466 [°] ↑2.4 ↑2.1 ↓3.5 NA miR-483 ↓3.2Apoptosis [82] miR-493 ↑2.1 ↓2.2Proliferation [83– 85] miR-499a ↓5.0 ↑2.3Proliferation [86] miR-504 ↓2.6 ↑2.0Proliferation, Apoptosis [87, 88] miR-579 ↑2.8 NAmiR-582 [^] ↑2.4Proliferation [89] miR-615 ↓2.1Proliferation, Invasion [90, 91] miR-652 ↑2.4Proliferation, EMT [92, 93] miR-669b ↓2.1 NA miR-669h ↓3.6 ↑2.3 NA miR-669i ↓2.3 NA miR-669k ↓7.2 ↓5. [score:3]
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[+] score: 2
Kumar et al. pointed out that the human TP53 gene can be negatively regulated by several miRNAs: miRNA-125b, miRNA-504, miRNA-25, and miRNA-30d [30]. [score:2]
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20
[+] score: 1
Among them, 4 miRNAs were induced in common between these two dosage exposures, i. e., miR-504-3p, miR-1927, miR-6401, and miR-1892. [score:1]
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