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5 publications mentioning dre-mir-184-2

Open access articles that are associated with the species Danio rerio and mention the gene name mir-184-2. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 393
Exogenous hsa-miR-184 expression was remarkably up-regulated in cells transfected with hsa-miR-184 mimic (Figure 3A), and endogenous hsa-miR-184 expression was down-regulated in cells transfected with hsa-miR-184 inhibitor (Figure 3B). [score:13]
C-F. Proliferative rates of ARPE-19 cells transfected with NC mimic (C), hsa-miR-184 mimic (C), NC inhibitor (E), and hsa-miR-184 inhibitor (E), and migration of ARPE-19 cells transfected with NC mimic (D), hsa-miR-184 mimic (D), NC inhibitor (F), and hsa-miR-184 inhibitor (F). [score:9]
Q-PCR results indicated that knocking down of dre-miR-184 will suppress the expression of RPE markers, while overexpression of dre-miR-184 can promote RPE development (Figures 4C-4D). [score:9]
Ectopic hsa-miR-184 overexpression elevated both mRNA and protein expressions of the RPE markers (Figures 3C, 3E-3F), while hsa-miR-184 insufficiency suppressed their expressions (Figures 3D, 3E, and 3G). [score:9]
Human and zebrafish miRNA mimics and inhibitors, including NC mimic, NC inhibitor, hsa-miR-184 mimic, hsa-miR-184 inhibitor, dre-miR-184 mimic, and dre-miR-184 inhibitor, were purchased from GenePharma Co. [score:9]
C-F. Four differentially expressed miRNAs with fold change of over 2 among all time points, including the up-regulated hsa-miR-184 (C), hsa-miR-449a (D), hsa-miR-449b-5p (E), and the down-regulated hsa-miR-302d-3p (F), were selected for validation of the microarray results in hiPSC-RPE at 0, 30, 60, and 90 dpd. [score:9]
AKT2 is a direct target of hsa-miR-184 in RPE cellsPrevious study suggested that hsa-miR-184 suppressed AKT2 expression in neuroblastoma [24]. [score:8]
Both proliferation and migration were inhibited by hsa-miR-184 overexpression at all time points post transfection (Figures 6C-6D), and cell proliferative and migratory rates were increased in cells with endogenous hsa-miR-184 down-regulated (Figures 6E-6F). [score:8]
Altogether, our findings supported that hsa-miR-184 directly targets AKT2 3′-UTR and suppresses AKT2 expression in RPE. [score:8]
Figure 7Hsa-miR-184 is down-regulated in dysfunctional RPE, and AKT2 is up-regulated in AMD A. Relative RNA expressions of hsa-miR-184, AKT2, RPE65, RLBP1, BEST1, and LRAT in the macular RPE of an aged donor compared to a young donor. [score:8]
G-H. Relative mRNA expressions of MITF, RPE65, RLBP1, LRAT, BEST1, KRT18, and CTNNB1 in hiPSC-RPE at 30 dpd transfected with hsa-miR-184 mimic plus empty expression vector compared to hsa-miR-184 mimic plus AcFlag-AKT2 (G), and in cells transfected with hsa-miR-184 inhibitor plus scramble siRNA compared hsa-miR-184 inhibitor plus AKT2-siRNA (H). [score:7]
Hsa-miR-184 is down-regulated in dysfunctional RPE, and AKT2 is up-regulated in AMD. [score:7]
Agreed with the microarray data, hsa-miR-184, hsa-miR-449a and hsa-miR-449b-5p were consistently up-regulated along with the differentiation, while hsa-miR-302d-3p was down-regulated (Figures 1C-1F). [score:7]
In the present study, we confirm that AKT2 is a direct target for miR-184 in ARPE-19 cells, and miR-184 promotes RPE differentiation via suppression of AKT2. [score:6]
Figure 4Dre-miR-184 promotes retinal development in vivo A-B. Relative expression of dre-miR-184 in zebrafish injected with dre-miR-184 inhibitor compared to NC inhibitor (A), and in embryos injected with dre-miR-184 mimic compared with NC mimic (B). [score:6]
MiR-184 -based supplementary therapeutics and mTOR pathway inhibitor, like rapamycin, can inhibit RPE dedifferentiation in dry AMD and may become prospective options for treating retinal degenerative diseases. [score:6]
Q-PCR analysis revealed that overexpression of exogenous hsa-miR-184 down-regulates the AKT2 mRNA level in 30 dpd hiPSC-RPE (Figure 5C). [score:6]
Hsa-miR-184 targets the AKT2/mTOR pathway, and inhibits cell proliferation and migration. [score:5]
The mutated miR-184 antagonizes miR-205 to maintain the expression of the inositol polyphosphate phosphatase-like 1 (INPPL1) gene, which generates the disease phenotype [19]. [score:5]
We further aimed to tell whether the effect of hsa-miR-184 on AKT2 expression is a direct effect of hsa-miR-184 targeting AKT2 3′-UTR using luciferase reporter assay. [score:5]
Overexpression of miR-184 promotes RPE differentiation, while miR-184 insufficiency could suppress RPE differentiation. [score:5]
Taken together, our results suggested that hsa-miR-184 suppresses the AKT2/mTOR signaling pathway, and inhibits cell proliferation and migration. [score:5]
Embryos at 1- to 2-cell stage (0 dpf) were grouped and injected with 1 nl solution containing 4 μM the abovementioned NC mimic, NC inhibitor, dre-miR-184 mimic, or dre-miR-184 -inhibitor, respectively. [score:5]
As shown in Figure 6A, western blot analysis revealed decreased phosphorylation of AKT2 [Ser474], mTOR [Ser2448], and p70S6K [Thr389] in 30 dpd hiPSC-RPE overexpressing hsa-miR-184, suggesting that hsa-miR-184 could inhibit the AKT2/mTOR pathway. [score:5]
A-B. Relative expression of dre-miR-184 in zebrafish injected with dre-miR-184 inhibitor compared to NC inhibitor (A), and in embryos injected with dre-miR-184 mimic compared with NC mimic (B). [score:5]
Figure 5Hsa-miR-184 targets the AKT2/mTOR pathway, and inhibits cell proliferation and migration A. Schematic construction of reporter containing a fragment of the wild type and mutant AKT2 3′-TUR. [score:5]
Previous study suggested that hsa-miR-184 suppressed AKT2 expression in neuroblastoma [24]. [score:5]
A-B. Relative miRNA expression of hsa-miR-184 in hiPSC-RPE at 30 dpd transfected with hsa-miR-184 mimic compared to NC mimic (A), and in cells transfected with hsa-miR-184 inhibitor compared to NC inhibitor (B). [score:5]
Since hsa-miR-184 could inhibit mTOR, we, therefore, assumed that hsa-miR-184 expression will be reduced in dysfunctional RPE. [score:5]
C-D. Relative mRNA expressions of RPE65, RLBP1, MERTK, BEST1, and TJP1 in hiPSC-RPE at 30 dpd transfected with hsa-miR-184 mimic compared to NC mimic (C), and in cells transfected with hsa-miR-184 inhibitor compared to NC inhibitor (D). [score:5]
As above mentioned, hsa-miR-184 expression was consistently increased along with RPE differentiation (Figure 1C), we then respectively transfected hsa-miR-184 mimic and inhibitor into hiPSC-RPE at 30 dpd to see its role on cell differentiation. [score:5]
Hsa-miR-184 suppresses the AKT2/mTOR pathway, and inhibits cell proliferation and migration. [score:5]
Figure 3 A-B. Relative miRNA expression of hsa-miR-184 in hiPSC-RPE at 30 dpd transfected with hsa-miR-184 mimic compared to NC mimic (A), and in cells transfected with hsa-miR-184 inhibitor compared to NC inhibitor (B). [score:5]
Embryos at 1- to 2-cell stage were individually injected with dre-miR-184 mimic or inhibitor to modulate its exogenous or endogenous dre-miR-184 expression (Figures 4A-4B). [score:5]
E-G. Relative protein expressions of MERTK, LRAT, ZO-1, Keratin 18, RLBP1, and β-catenin in hiPSC-RPE at 30 dpd transfected with hsa-miR-184 mimic compared to NC mimic (E-F), and in cells transfected with hsa-miR-184 inhibitor compared to NC inhibitor (E, G). [score:5]
AKT2 expression was found consistently decreased along with the differentiation from hiPSC to RPE as demonstrated in Figure 5D, which was inversely correlated to the expression pattern of hsa-miR-184 (Figure 2C). [score:5]
C-D. Relative mRNA expressions of pax6a, rpe65c, rlbp1b, lrat, mertka, best1, krt18, cdh2, tjp1b, and ctnnb1 in zebrafish injected with dre-miR-184 inhibitor compared to NC inhibitor (C), and in embryos injected with dre-miR-184 mimic compared with NC mimic (D). [score:5]
Our results were consistent with the previous report that hsa-miR-184 expression was inhibited in the RPE of donors with AMD [19], and further implied that hsa-miR-184 may play a role in keeping regular function of RPE. [score:5]
We have also reasoned that miR-184 suppresses the AKT2/mTOR signaling pathway, promotes RPE differentiation, and inhibits RPE proliferation and migration. [score:5]
As indicated above, hsa-miR-184 would promote RPE differentiation, and AKT2 was a direct target of hsa-miR-184. [score:4]
Antisense hsa-miR-184 oligonucleotides are used as hsa-miR-184 inhibitor, which binds directly to the single strand mature hsa-miR-184 to block its activity [26]. [score:4]
Our findings suggested that dre-miR-184 functions in maintaining the regular function of zebrafish RPE, and its insufficiency would suppress RPE development. [score:4]
Hsa-miR-184 was constantly up-regulated along with the differentiation from hiPSC to RPE. [score:4]
Mature miR-184, containing 22 nucleotides, shows tissue and developmental stage specific expression patterns [17, 18]. [score:4]
Consistent to mRNA findings, immunofluorescence revealed decreased reactivity of retinoid isomerohydrolase (encoded by rpe65c; NP_000320), a marker of RPE cells, in the RPE layer of zebrafish injected with dre-miR-184 inhibitor (Figures 4E-4H) compared to embryos injected with NC inhibitor (Figures 4I-4L). [score:4]
As expected, hsa-miR-184 level was found remarkably down-regulated in the aged donor with RPE dysfunction (Figure 7A). [score:4]
Dre-miR-184 insufficiency suppresses RPE development in vivo. [score:4]
This finding implies that in order to sustain RPE function and survival, miR-184 may also modulate the expressions of regulatory factors, like other miRNAs and long non-coding RNAs. [score:4]
A total of 78 miRNAs are initially sorted out, among which miR-184 is the most up-regulated signature along with the differentiation, and its crucial role in RPE differentiation is further confirmed in both cellular and zebrafish mo dels. [score:4]
AKT2 is a direct target of hsa-miR-184 in RPE cells. [score:4]
Reduction in miR-184 expression will decrease level of EZR-bounded LAMP-1 and interrupt RPE phagocytosis [19]. [score:3]
Since cellular proliferation and migration can follow the dedifferentiation of postmitotic tissues, including RPE, and activation of mTOR pathway have been reported to enhance cell proliferation and migration [16, 27– 30], we next determined whether hsa-miR-184 would inhibit proliferation and migration of ARPE-19 cells. [score:3]
Hsa-miR-184 is decreased in dysfunctional RPE, and AKT2 is increased in AMDActivation of mTOR signaling pathway is reported to cause RPE dedifferentiation and retinal degenerative diseases, namely AMD [1]. [score:3]
Previous study has revealed that miR-184 expression is decreased in RPE of AMD donors [19]; however, its role in AMD pathogenesis, especially in RPE dedifferentiation, is still largely unknown. [score:3]
via suppression of AKT2We next tested whether AKT2 could affect the promotive effect of hsa-miR-184 on RPE differentiation. [score:3]
Hsa-miR-184 mimic comprises chemically synthesized oligonucleotides identical to the sequence of endogenous hsa-miR-184, which will be loaded into the RNA -induced silencing complex (RISC) and silence target genes like endogenous hsa-miR-184 [25]. [score:3]
Collectively, our data implied that hsa-miR-184 promotes RPE differentiation via suppression of AKT2. [score:3]
Ezrin (EZR) gene is the only reported target of miR-184 involved in RPE functions. [score:3]
Herein, consistent to previous findings, we show that miR-184 expression is remarkably reduced in the macular RPE of a donor with RPE dysfunction, indicating its role in maintaining regular functions of RPE cells. [score:3]
Initial assessments were carried out to see whether AKT2 expression levels are inversely related to hsa-miR-184 levels. [score:3]
We also demonstrate that miR-184 blocks the AKT2/mTOR signaling pathway and suppresses cell proliferation and migration. [score:3]
Taken together, our study concludes that miR-184 promotes RPE differentiation via inhibiting the AKT2/mTOR signaling pathway, and miR-184 insufficiency plays an important role in the pathogenesis of dry AMD. [score:3]
RNA isolation, RT-PCR, and real-time PCR were carried out to determine the expression levels of dre-miR-184 and several RPE markers. [score:3]
C. mRNA expression of AKT2 were analyzed in 30 dpd hiPSC-RPE transfected with NC mimic or hsa-miR-184 mimic, respectively. [score:3]
Hsa-miR-184 promotes RPE differentiation via suppression of AKT2. [score:3]
Cellular mo del also proves that the expression level of miR-184 associates with RPE differentiation. [score:3]
We showed that AKT2 overexpression abrogated the hsa-miR-184 mediated RPE differentiation (Figure 5F). [score:3]
AKT2 has been proved as a target for miR-184 in neuroblastoma cell line [24], while their interaction in RPE cells remains inclusive. [score:3]
Dre-miR-184 insufficiency suppresses RPE development in vivoWe next used zebrafish mo del to investigate the role of dre-miR-184 on RPE development. [score:3]
RAC-beta serine/threonine-protein kinase (AKT2; NM_001626) was found as a target for hsa-miR-184 (Figure 2G) [24]. [score:3]
We then focused on studying whether AKT2 is a potential target of hsa-miR-184 in RPE cells. [score:3]
By contrast, the dre-miR-184 mimic injection group showed robust expression of retinoid isomerohydrolase in the RPE layer (Figures 4M-4P), similar to the NC mimic injection group (Figures 4Q-4T). [score:3]
To confirm that AKT2 was inhibited by hsa-miR-184 in RPE, we next measured the expression of AKT2 in 30 dpd hiPSC-RPE transfected with hsa-miR-184 mimic. [score:3]
Further, silencing of AKT2 rescued the inhibition on RPE differentiation induced by hsa-miR-184 insufficiency (Figure 5F). [score:3]
Dre-miR-184 promotes retinal development in vivo. [score:2]
To test our hypothesis, we compared the expression of hsa-miR-184 between the macular RPE of a 70-year-old male and a 30-year-old female donor. [score:2]
B. Schematic of the hsa-miR-184 regulatory network. [score:2]
The impact of miR-184 on promoting RPE development is further confirmed in zebrafish mo del. [score:2]
Other than retinopathy, miR-184 seed region mutations are reported to cause EDICT syndrome, presenting familial keratoconus with cataract [35, 36]. [score:2]
Since hsa-miR-184 was reported to present a decreased expression pattern in AMD patients, we next tested and compared the macular and extramacular AKT2 mRNA levels in RPE-choroid from normal individuals and AMD patients. [score:2]
A. Relative RNA expressions of hsa-miR-184, AKT2, RPE65, RLBP1, BEST1, and LRAT in the macular RPE of an aged donor compared to a young donor. [score:2]
A fragment from the 3′-UTR of the AKT2 gene bearing its binding region with has-miR-184 were synthesized and cloned into the firefly pMIR-GLO™ luciferase vector (pMIR, Invitrogen) using SacI and XhoI restriction sites to construct the recombinant plasmid AKT2 [WT] and AKT2 [MU]. [score:1]
Hsa-miR-184 is decreased in dysfunctional RPE, and AKT2 is increased in AMD. [score:1]
The role of miR-184 in AMD pathogenesis, especially in RPE dedifferentiation, is still largely unknown. [score:1]
Reduction in RPE markers is observed in embryos with miR-184 silenced. [score:1]
In addition, abnormal methylation status of MIR-184 has also been found correlated with Rett syndrome, presented with autism spectrum disorders and involving irregular synaptic plasticity [18]. [score:1]
However, introduction of 3 single nucleotides located in the core binding region of AKT2 completely abolished the ability of hsa-miR-184 mimic to decrease luciferase activity (Figure 5B). [score:1]
A. of p-AKT2, AKT2, p-mTOR, mTOR, p-p70S6K, p70S6K in 30 dpd hiPSC-RPE transfected with NC mimic/hsa-miR-184 mimic. [score:1]
Hsa-miR-184 promotes RPE differentiation. [score:1]
We therefore hypothesized that hsa-miR-184 might promote RPE differentiation via blocking the AKT2/mTOR signaling pathway (Figure 6B). [score:1]
Our findings suggested that hsa-miR-184 promotes the differentiation of hiPSC-RPE. [score:1]
Hsa-miR-184 promotes cell differentiation. [score:1]
Further analysis suggested that, opposite to the decreased hsa-miR-184 level, AKT2 mRNA was elevated in the macular RPE of the above mentioned aged donor with RPE dysfunction (Figure 7B). [score:1]
Thus, deep investigations into the regulatory network and epigenetic regulation of miR-184 in maintaining RPE function may become part of our future work. [score:1]
In this study, we aim to analyze the effect of miR-184 in RPE differentiation. [score:1]
We next tested whether AKT2 could affect the promotive effect of hsa-miR-184 on RPE differentiation. [score:1]
Figure 6 A. of p-AKT2, AKT2, p-mTOR, mTOR, p-p70S6K, p70S6K in 30 dpd hiPSC-RPE transfected with NC mimic/hsa-miR-184 mimic. [score:1]
Further work is still warranted to better elucidate the role of miR-184 in AMD pathogenesis. [score:1]
A fragment from the 3′-UTR of the AKT2 gene bearing its binding region with hsa-miR-184 was cloned into the firefly pMIR-GLO™ luciferase vector (pMIR, Invitrogen) to construct the recombinant plasmid AKT2 [WT] (Figure 5A). [score:1]
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[+] score: 30
Other miRNAs from this paper: hsa-mir-23a, hsa-mir-29a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-205, hsa-mir-214, hsa-mir-221, hsa-mir-1-2, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-184, hsa-mir-193a, hsa-mir-1-1, hsa-mir-29c, hsa-mir-133b, dre-mir-205, dre-mir-214, dre-mir-221, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-mir-1-2, dre-mir-1-1, dre-mir-23a-1, dre-mir-23a-2, dre-mir-23a-3, dre-mir-29b-1, dre-mir-29b-2, dre-mir-29a, dre-mir-107a, dre-mir-122, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-184-1, dre-mir-193a-1, dre-mir-193a-2, dre-mir-202, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, hsa-mir-202, hsa-mir-499a, dre-mir-499, dre-mir-724, dre-mir-725, dre-mir-107b, dre-mir-2189, hsa-mir-499b, dre-mir-29b3
This network visualization shows that (1) all modules contain at least 2 genes that are predicted targets of a deregulated miRNA identified in this study, except the module “Apoptosis and NAFLD”; (2) dre-miR-2189, the only DE miRNA that was downregulated, targets many genes in modules that are predominantly upregulated such as Cell cycle (4 target mRNAs), Apoptosis and Autophagy (19 targets), Epigenetics and Apoptosis/Autophagy (2 targets) and Receptors (4 targets); (3) certain miRNAs have only 1 target gene in the selected modules, including dre-miR-184 (“Oxidative phosphorylation”), dre-miR-430a and dre-miR-430b (“Apoptosis and Autophagy”); (4) while other miRNAs have common target genes in the same modules, i. e., dre-miR-725/dre-miR-724/dre-miR-193a, dre-miR-202, dre-miR-205 and dre-miR-133a that have several common target genes in modules “Oxidative phosphorylation and NAFLD”, “Apoptosis/Autophagy”, “NAFLD” and “Cell cycle”. [score:26]
Here we showed that dre-miR-724 and -725 teamed up with dre-miR-193a, -202, -205 and -133a to regulate apoptosis, autophagy, NAFLD, oxidative phosphorylation and cell cycle modules whereas other miRNAs only had one target in a single module (dre-miR-184, -430a, -430b). [score:4]
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[+] score: 8
Similarly, miR-184 was expressed primarily in testis, which probably was involved in the post-transcription regulation of nuclear receptor corepressor 2 (Ncor2) in mammalian spermatogenesis [24]. [score:4]
Wu J. Bao J. Wang L. Hu Y. Xu C. MicroRNA-184 downregulates nuclear receptor corepressor 2 in mouse spermatogenesisBMC Dev. [score:3]
The role of specific miRNAs such as miR-15a, miR-184, and miR-384 is demonstrated in the process of spermatogenesis. [score:1]
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[+] score: 3
Furthermore, the top 5 most abundant miRNA families expressed at each stage were selected, including dre-let-7a, dre-miR-1, dre-miR-10a-5p, dre-miR-124, dre-miR-181a-5p, dre-miR-184, dre-miR-192, dre-miR-22a, dre-miR-25, dre-miR-430a and dre-miR-456 families (Figure  5C). [score:3]
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[+] score: 3
We also performed analogous experiments in Drosophila S2R+ cells with two predicted targets of miR-184 (PCK and CG13088), and revealed that both of these MREs are functional in this cell type (Supplementary Fig. 1). [score:3]
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