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5 publications mentioning hsa-mir-4732

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-4732. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 170
d Total cell number of primary CD34 erythroid progenitors 24 h after equal numbers of cells were transfected with indicated combinations of microRNA mimics and overexpression constructs on day 8 of differentiation (n = 3) (* p < 0.05, ** p < 0.01)Given the ability to suppress TGF-β signaling activity, we hypothesized that miR-4732-3p may promote proliferation by suppressing SMAD2 and SMAD4. [score:7]
This regulation occurs through the predicted target miR-4732-3p binding sites, as mutation of the respective target sequences in the 3’ UTR of SMAD2 and 4 abrogated the endogenous microRNA -mediated luciferase repression (Fig.   4d). [score:7]
d Total cell number of primary CD34 erythroid progenitors 24 h after equal numbers of cells were transfected with indicated combinations of microRNA mimics and overexpression constructs on day 8 of differentiation (n = 3) (* p < 0.05, ** p < 0.01) Given the ability to suppress TGF-β signaling activity, we hypothesized that miR-4732-3p may promote proliferation by suppressing SMAD2 and SMAD4. [score:7]
Using the microRNA target prediction tool Targetscan [11], 556 genes were predicted to be regulated by miR-4732-3p (Additional file 7: Table S6). [score:6]
Overexpression of miR-4732-3p significantly reduced the expression of all these SMAD4-regulated genes (Fig.   5b). [score:6]
The fold change of expression for each treatment group was first normalized to alpha tubulin input for that treatment, then ratio set relative to the control treatmentTo understand the in vivo relevance of the regulatory relationship between miR-4732-3p and SMAD2/SMAD4, we determined whether miR-4732-3p inhibits the protein levels of SMAD2 and SMAD4 (Fig.   4e-f). [score:6]
The fold change of expression for each treatment group was first normalized to alpha tubulin input for that treatment, then ratio set relative to the control treatment To understand the in vivo relevance of the regulatory relationship between miR-4732-3p and SMAD2/SMAD4, we determined whether miR-4732-3p inhibits the protein levels of SMAD2 and SMAD4 (Fig.   4e-f). [score:6]
Upregulation of miR-4732-3p, as well as its physical proximity to the miR-144/451 locus suggests its similar regulation and functional role during erythroid development. [score:6]
Though other mRNA targets and phenotypes associated with miR-4732-3p have yet to be elucidated, miR-4732-3p represents a unique, endogenous TGF-β signaling inhibitor that promotes erythroid expansion, and has the potential to be manipulated as a biomarker or novel therapeutic for various anemia disorders. [score:5]
Overexpression of miR-4732-3p in K562s resulted in a significant reduction in relative reporter luciferase values (Fig.   5a), demonstrating that miR-4732-3p suppresses SMAD4 -mediated transcription activities. [score:5]
To determine whether endogenous miR-4732-3p repression would affect reporter expression, we inhibited miR-4732-3p with an antisense oligonucleotide (ASO) and observed increased relative Renilla reporter activities for both SMAD2 and SMAD4 (Figs.   4c). [score:5]
For microRNA inhibition, miR-4732-3p antisense 2’-O-Methyl oligonucleotide (AMO) or non -targeting (NT) antisense 2’-O-Methyl oligonucleotide (Dharmacon) were used. [score:5]
Additionally, we determined whether miR-4732-3p overexpression may affect the level of SMAD4 -dependent target genes, such as pai-1, p21, bim, and bax [42, 43]. [score:5]
List of predicted targets for miR-4732-3p in Targetscan. [score:5]
Thus, miR-4732-3p inhibits the protein levels of both SMAD2 and SMAD4 through a canonical microRNA -mediated regulation of 3’ UTRs. [score:4]
Next, we assessed whether miR-4732-3p -mediated downregulation of SMAD2 and SMAD4 would affect TGF-β signaling. [score:4]
However, miR-4732-5p levels were less dramatically upregulated during erythropoiesis. [score:4]
Within the miR-144/451 locus previously implicated in erythroid development, we observed unique co -expression of several primate-specific noncoding RNAs, including a lncRNA, and miR-4732-5p/-3p. [score:4]
Similar to miR-451a and miR-144-3p [8], both miR-144-5p and miR-4732-3p were also upregulated during erythropoiesis (Fig.   3b). [score:4]
The 3’UTR mutated reporters were constructed using the QuikChange II Site-Directed Mutagenesis kit (Stratagene, CA) to mutate the predicted targets of the miR-4732-3p seed sequence. [score:4]
MiR-4732-3p microRNA mimic or non -targeting (NT) microRNA mimic #1 (Dharmacon) were used for microRNA overexpression. [score:4]
In the second pattern, we observed co -expression a long RNA spanning only the 5’ portion of the miR-4732 pre-microRNA, proximal to the miR-144/451 region; this lncRNA was confirmed via RT-PCR (Additional file 1: Figure S4). [score:3]
Transfection of miR-4732-3p mimics in K562s reduced the protein levels of both SMAD2 and SMAD4 (Fig.   4e), whereas inhibition of miR-4732-3p increased the levels of SMAD2 and SMAD4 protein (Fig.   4f). [score:3]
In this study, we demonstrated that miR-4732-3p inhibits TGF-β signaling to promote erythroid cell expansion during differentiation. [score:3]
We used real-time PCR to determine the expression dynamics of miR-4732-3p and other erythrocyte microRNAs at different time points during in vitro differentiation of CD34+ erythroid progenitors (Fig.   3b). [score:3]
Consistent with this hypothesis, overexpression of miR-4732-3p in differentiating CD34+ erythroid progenitors resulted in a significant increase in total cell number (Fig.   5c). [score:3]
Second, miR-4732-3p is much more highly expressed than miR-4732-5p. [score:3]
a Alignment of miR-4732-3p and predicted target sites in the 3’ UTR of SMAD2 and SMAD4, with mutated binding sites underlined. [score:3]
Furthermore, the miR-4732-3p -mediated increase in cell number was abolished by overexpression of SMAD2 and SMAD4 with cDNA constructs lacking miR-4732-3p-responsive 3’UTRs (Fig.   5d). [score:3]
b Expression of miR-144-5p, miR-4732-3p, and miR-4732-5p, during CD34+ erythroid differentiation using progenitors from three different individuals. [score:3]
We show that miR-4732-3p targets both SMAD2 and SMAD4, two critical components of the TGF-β pathway implicated in erythropoiesis. [score:3]
For luciferase reporter constructs, a portion of the 3' untranslated region (UTR) of SMAD2 and SMAD4 flanking the predicted miR-4732-3p binding site was amplified and cloned into the XhoI and NotI sites downstream of Renilla luciferase in the psiCheck-2 vector (Promega). [score:3]
Finally, functional studies demonstrate the primate-specific microRNA miR-4732-3p regulates the TGF-β pathway during human erythropoiesis. [score:2]
MiR-4732-3p was predicted to target both SMAD2 and SMAD4 [11], components of the TGF-β pathway instrumental in fine-tuning proliferation for efficient erythropoiesis [12]. [score:2]
As shown, transfection with a miR-4732-3p mimic significantly repressed normalized Renilla 3’ UTR reporter activities of both SMAD2 and SMAD4 in K562s, indicating the ability of miR-4732-3p to regulate SMAD2/4 (Fig.   4b). [score:2]
SMAD2 and SMAD4 are both predicted to be regulated by miR-4732-3p, with conserved seed sequence binding sites in most species. [score:2]
MiR-4732-3p directly regulates SMAD2 and SMAD4. [score:2]
miR-4732-3p regulates the TGF-β signaling cascade. [score:2]
Our study presents the most extensive profiling of erythrocyte RNAs to date, and describes primate-specific interactions between the key modulator miR-4732-3p and TGF-β signaling during human erythropoiesis. [score:1]
U6 snRNA was used as a loading control, with fold difference set relative to day 6. c Predicted folding structure for the miR-4732 pre-microRNA according to miRDeep, and frequency of reads for mature microRNAs from one representative sample. [score:1]
Here we focus on the primate-specific miR-4732-3p. [score:1]
We found that miR-4732-3p is an abundant erythrocyte microRNA within the erythroid-enriched miR-144/451 locus. [score:1]
These results indicated that miR-4732-3p increased erythroid cell number by repressing the levels of SMAD2/4. [score:1]
d Sequence conservation of miR-4732-3p in listed species. [score:1]
Mir-4732-3p provides an additional layer of regulation for primate erythropoiesis. [score:1]
The most prevalent mature read sequences for miR-4732-3p (red) and miR-4732-5p (blue) are shown. [score:1]
In addition, the lncRNA overlapping miR-4732 may exist as a truncated form of a longer RNA precursor which undergoes further processing for production of the adjacent microRNAs within this locus. [score:1]
MirDeep maps miR-4732 to a predicted pre-microRNA canonical stem-loop folding structure with distinct 5p- and 3p- mature sequence reads (Fig.   3c), indicative of a bona fide microRNA. [score:1]
Furthermore, miR-4732-3p represses SMAD2/4 -dependent TGF-β signaling, thereby promoting cell proliferation during erythroid differentiation. [score:1]
RT-PCR validation of lncRNA spanning miR-4732 precursor. [score:1]
Together, the significant miRDeep score (1.9), predicted pre-microRNA structure, and proximity to the miR-144/451 locus underscores the authenticity and potential functional relevance of miR-4732-3p. [score:1]
Together, these data are consistent with the possibility that miR-4732-3p modulates TGF-β signaling to promote erythroid cell survival and production during erythropoiesis. [score:1]
These RNAs include a ~250 nt lncRNA spanning the 5’ hairpin region of pre-miR-4732, as well as miR-4732-5p and-3p (Fig.   3a). [score:1]
Interestingly, miR-4732-3p is primate-specific, with full seed sequence identical only among primates. [score:1]
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2
[+] score: 10
Further analysis demonstrated that hsa-miR-144-5p expression was highly correlated with hsa-miR-4732-5p and hsa-miR-451a expression, and low hsa-miR-144-3p and hsa-miR-144-5p expression was shown to be the independent risk factors for the onset of esophageal carcinoma. [score:7]
Pearson correlation analysis demonstrated that the expression levels of individual miR-144/451 cluster members were correlated with each other, except for hsa-miR-144-3p and hsa-miR-4732-3p. [score:3]
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[+] score: 5
In contrast, eight miRNAs (hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-410-3p, hsa-miR-4732-3p and hsa-miR-6741-3p) had no experimentally validated targets described to date. [score:3]
In conclusion, we identified 24 novel differentially abundant miRNAs in the plasma of patients with class IV lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p, hsa-miR-6741-3p) that are good candidates for further assessment as diagnostic biomarkers of class IV lupus nephritis. [score:1]
Alterations in the relative abundance of miR-589-3p, miR-1260b, miR-4511, miR-485-5p, miR-584-5p, miR-543, miR-153-3p, miR-6087, miR-3942-5p, miR-7977, miR-323b-3p, miR-4732-3p and miR-6741-3p, and its possible association with lupus nephritis is described for the first time. [score:1]
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[+] score: 1
One has no known homolog in cow (hsa-miR-4732-3p). [score:1]
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5
[+] score: 1
Even though a putative binding site for Has-mir-4732-5p was obtained at this variant's nucleotide position from miRBase database, further in silico analysis by RNAhybrid tool gave a very weak binding probability. [score:1]
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