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33 publications mentioning hsa-mir-517a

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-517a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 186
Also, overexpression of TNIP1 did not completely block miR-517a/c induced expression of TNF and IL8. [score:5]
Similarly, miR-517a/c increased target gene expression (IL8, IL6 and TNF) in a p65 -dependent manner and increased p65 nuclear translocation (see Additional file 2, Figure S2). [score:5]
Consistent with these results, miR-517a/c induced the expression of endogenous NF-κB targets and promoted the nuclear localization of p65 and the degradation of IκB. [score:5]
Therefore, we deduced the likely target of miR-517a/c was an inhibitor of NF-κB signaling. [score:5]
According to TargetScan predictions [45], this shift results in base-pairing between TNIP1 and nucleotides 2 to 7 of miR-517b as opposed to nucleotides 2 to 8 in miR-517a/c-the latter resulting in a more favorable miRNA-target interaction. [score:5]
While there was a significant increase in TNIP1 expression, miR-517a/c expression was not significantly changed (see Additional file 2, Figure S4). [score:5]
Lastly, given that TNIP1 is a TNF regulated gene [27] and miRNAs are common in feedback regulation, we hypothesized that NF-κB regulates miR-517a/c which in turn activates the pathway through knockdown of TNIP1. [score:5]
Figure 5 TNIP1 is the direct functional target of miR-517a/c. [score:4]
TNIP1 is a direct functional target of miR-517a/c. [score:4]
While knockdown of TNIP1 was sufficient to induce expression of TNF and IL8 as much as 18- and 56-fold, respectively (Figure 5B), miR-517a/c were more potent inducers (Figure 4B). [score:4]
Also, miR-517b did not phenocopy miR-517a/c in secondary screens (Figure 3A) or knockdown TNIP1 protein expression (Figure 5A). [score:4]
These results suggested that miR-517a/c interact directly with TNIP1 and that the minor allele of SNP rs72558377 decreases miRNA-target interaction and consequently miR-517a/c mediated repression of TNIP1. [score:4]
Next, we selected representative miRNAs for secondary screening: those that activated the reporter in the -TNF screen (miR-517a, miR-517c), inhibited the reporter in the +TNF screen (miR-210, miR-375), or activated the reporter in both screens (miR-483). [score:3]
Effect of miR-517 family on endogenous NF-κB targets and signaling components. [score:3]
This was likely because miR-517a/c had about eight times fewer predicted targets than the other miRNAs (see Additional file 1, Table S3). [score:3]
miR-517a/c, but not miR-517b, increased nuclear p65 and decreased cytoplasmic IκB-α expression relative to the negative control (Figure 4D). [score:3]
Finally, we hypothesized that overexpression of TNIP1 would block the effect of miR-517a/c. [score:3]
We decided to follow up on the miR-517 family with additional experiments for several reasons: 1) miRNAs typically have a moderate impact on their targets yet miR-517a/c were potent activators of reporter activity in the absence of any added stimulus; 2) we were intrigued that miR-517b did not activate signaling despite extensive sequence similarity to miR-517a/c; and 3) a previous proteomics study by Luo et al. suggested miR-517a involvement in MAPK and TNF signaling in BeWo cells [23]. [score:3]
Further studies are needed to elucidate additional miR-517a/c targets. [score:3]
Co-transfection of the TNIP1 construct with the miRNA mimics reduced miR-517a/c -induced expression of IL8 and TNF in HEK293 cells (Figure 5C). [score:3]
As miR-517a/c are suppressed in most cell/tissue types, their reported activation by demethylating drugs, such as 5-aza-2′-deoxycytidine (5-aza-dc) [56] may have therapeutic value in the treatment of certain cancers. [score:3]
Both siRNAs reduced miR-517a/c induced expression of IL8 and TNF at least 6-fold (Figure 4D; P ≤0.01). [score:3]
Hence, the shift in the miR-517b seed likely alters target interaction relative to miR-517a/c. [score:3]
Next, we wanted to test the effect of the miR-517 miRNAs on endogenous NF-κB targets. [score:3]
Next, we tested if siRNAs targeting TNIP1 could phenocopy miR-517a/c. [score:3]
In unstimulated cells, miR-517a/c strongly induced IL8 (>160-fold) and TNF (>40-fold) expression while miR-517b had only a modest effect (13- and 4-fold, respectively), confirming the reporter results (Figure 3A). [score:3]
However, in cells treated with TNF, there was no significant change in IL8 and TNF expression in cells transfected with the miR-517 mimics relative to the negative control (Figure 4C). [score:3]
With this method, we derived high confidence candidate targets for all the miRNAs with the exception of miR-517a/c. [score:3]
We tested this by creating a TNIP1 cDNA construct with a truncated 3'UTR lacking the miR-517a/c target site. [score:3]
Here, we show that the minor allele of SNP rs72558377 (T) creates a G-U base pair between miR-517a/c and TNIP1 that disrupts binding, resulting in reduced knockdown of TNIP1. [score:2]
Hence, our results suggest that the knockdown of TNIP1 by miR-517a/c may both activate NF-κB signaling and repress its anti-apoptotic activity. [score:2]
To confirm the assay results, we tested the effect of miR-517a/c on the cleavage of poly (ADP-ribose) polymerase 1 (PARP1), an endogenous CASP3 target. [score:2]
miRNAs, micro RNAs; PARP, poly(ADP-ribose) polymerase; siRNAs, small interfering RNAs; SD, standard deviation; TNIP1, tumor necrosis factor alpha -induced protein 3 interacting protein 1. Next, we tested if miR-517a/c induced apoptosis was a result of TNIP1 knockdown. [score:2]
This was due in part to the smaller number of total predicted targets for miR-517a/c compared to the other miRNAs (see Additional file 1, Table S3). [score:2]
Also, interestingly, Na et al. recently found miR-517a down-regulated in the placenta of patients with complete hydatidiform moles-a condition characterized by increased trophoblast proliferation [54]. [score:2]
miRNAs, micro RNAs; PARP, poly(ADP-ribose) polymerase; siRNAs, small interfering RNAs; SD, standard deviation; TNIP1, tumor necrosis factor alpha -induced protein 3 interacting protein 1. Next, we tested if miR-517a/c induced apoptosis was a result of TNIP1 knockdown. [score:2]
Lastly, we characterized the top hits, miR-517a/c, identified their target, and explored the relationship between their impact on NF-κB signaling and their regulation of apoptosis in the human embryonic kidney cell line HEK293 and the osteosarcoma cell line U-2 OS. [score:2]
To test the functional consequence of this SNP as well as demonstrate direct interaction between miR-517a/c and TNIP1, we cloned sequences containing the major and minor alleles immediately downstream of a firefly luciferase reporter. [score:2]
Also, these conflicting functions of miR-517a/c may reflect the complex role of NF-κB in the regulation of cell survival. [score:2]
Together, these results suggested that knockdown of TNIP1 contributes to the apoptosis inducing activity of miR-517a/c. [score:2]
Lastly, miR-517a/c induced apoptosis in vitro, which was phenocopied by knockdown of TNIP1. [score:2]
Similar to miR-517a/c, siRNA mediated knockdown of TNIP1 increased cell death in HEK 293 cells (Figure 6D). [score:2]
Further, miR-517a/c were identified as negative regulators in the Keklikoglou screen. [score:2]
miR-517a and miR-517c were the top hits, activating the reporter 86- and 126-fold, respectively. [score:1]
Finally, we questioned whether the apoptosis inducing effects of miR-517a/c were specific to cancer-derived/immortalized cell lines. [score:1]
To test this we treated HEK293 cells with TNF over time and measured expression of TNIP1 mRNA and miR-517a/c. [score:1]
We identified TNFAIP3 interacting protein1 (TNIP1) as a target and characterized a functional SNP in the miR-517a/c binding site. [score:1]
The TNIP1 3'UTR harbors a functional SNP in the miR-517a/c binding site. [score:1]
However, none of the activators confirmed in our secondary screen (miR-483, miR-517a and miR-517c) were hits in the Lu et al. study. [score:1]
Additional studies are needed to understand how survival signals differ in various cell types in response to miR-517a/c and the role NF-κB may play in this process. [score:1]
B and C, n = 3. E, n = 4. * P ≤0.05, ** P 0.01. miRNAs, micro RNAs; siRNAs, small interfering RNAs; SD, standard deviation; TNIP1, tumor necrosis factor alpha -induced protein 3 interacting protein 1. Next, we took a closer look at the genomic region corresponding to the miR-517a/c binding site in TNIP1. [score:1]
The miR-517 family consists of three highly homologous members, miR-517a, miR-517b, and miR-517c, yet intriguingly, miR-517b, was not a hit in the primary screen. [score:1]
An oncogenic role for miR-517a has been suggested in liver and brain tumors [28, 29]. [score:1]
B and C, n = 3. E, n = 4. * P ≤0.05, ** P 0.01. miRNAs, micro RNAs; siRNAs, small interfering RNAs; SD, standard deviation; TNIP1, tumor necrosis factor alpha -induced protein 3 interacting protein 1. Next, we took a closer look at the genomic region corresponding to the miR-517a/c binding site in TNIP1. [score:1]
Mimic 'miR-517a/c' contained equal amounts of miR-517a and miR-517c. [score:1]
We informed the curators of miRBase, and the unshifted sequence (identical to miR-517a) is the new reference for miR-517b (now miR-517b-3p) as of miRBase v17. [score:1]
Together, these results suggested that miR-517a/c induced apoptosis in HEK293 and U-2 OS cells. [score:1]
This suggests that the effect of miR-517a/c on NF-κB signaling may be mediated by other genes in the pathway in addition to TNIP1. [score:1]
Corroborating the primary screen results, miR-517a and miR-517c were potent activators (59- and 38-fold, respectively) of the reporter in the absence of TNF, but did not potentiate TNF induced reporter activity (Figure 3, A and B). [score:1]
Functional analysis of miR-517a/c in primary HUVECs; Figure S3. [score:1]
However, we found miR-517a/c induced apoptosis in the immortalized cell line HEK293, in the osteosarcoma cell line U-2 OS and in primary HUVECs. [score:1]
miR-517a/c induced cleavage of full length PARP1 while no cleaved PARP1 was observed in lysates of control cells (Figure 6C). [score:1]
Lastly, we conclude that miR-517a/c are pro-apoptotic and potent activators of NF-κB that function at least in part through TNIP1. [score:1]
The repression by the miR-517 miRNAs was significantly alleviated in the minor allele reporter (Figure 5F). [score:1]
Figure 6. (A) Microscope images of HEK293 and U-2 OS cells transfected with miR-517a/c. [score:1]
We transfected HEK293 cells with the miR-517 mimics and measured the expression of IL8 and TNF mRNA in unstimulated cells (Figure 4B) and in cells stimulated with TNF for three hours (Figure 4C). [score:1]
Corroborating our results, a study by Yoshitomi et al. found miR-517a induced apoptosis in the bladder cancer cell lines T24 and BOY [53]. [score:1]
Both miR-517a and miR-517c, but not miR-517b, potently reduced TNIP1 protein levels (Figure 5A). [score:1]
Interestingly, during the preparation of this study we examined sequence reads of the miR-517b locus from miRBase [46], the central repository for miRNA sequences, and found a variant identical to miR-517a. [score:1]
Hence, these results suggest that miR-517a/c can induce apoptosis in primary and immortalized cells. [score:1]
miR-517a and miR-517c differ by one nucleotide at position 12, and miR-517b is shifted by one nucleotide relative to miR-517a (Figure 4A). [score:1]
Hence, we evaluated the effect of miR-517a/c on the subcellular localization and expression of p65 and IκB-α in HEK293 cells. [score:1]
In all, these results confirmed the primary and secondary screen data that miR-517a/c, and not miR-517b, were potent activators of NF-κB signaling. [score:1]
miR-517a/c induce apoptosis in HEK293 and U-2 OS cells. [score:1]
miR-517a and miR-517c repressed the reporter containing the major allele variant but had no effect on the empty vector (Figure 5F). [score:1]
This ensured that the effects we saw were due to the activity of TNIP1 protein and not due to competition for miR-517a/c binding. [score:1]
The miR-517 family is located in a large, primate-specific miRNA cluster on human chromosome 19 (C19MC) [24]. [score:1]
For follow up studies, we focused on the role of primate specific miR-517a and miR-517c as potent inducers of NF-κB signaling. [score:1]
miR-517a/c activation has been shown to promote cell survival and induce oncogenesis [28, 29]. [score:1]
To verify that miR-517a/c were acting through the NF-κB pathway, we co -transfected the mimics with one of two independent small interfering RNAs (siRNAs) against the p65 subunit of NF-κB (efficacy of the siRNAs is demonstrated in Additional file 2, Figure S1). [score:1]
miR-517a/c increased CASP-3/7 activity 16-fold in HEK-293 cells and 8-fold in U-2 OS cells relative to the negative control (Figure 6B). [score:1]
The miR-517 miRNAs share extensive sequence homology. [score:1]
Statistical comparison is relative to cells transfected with miR-517a/c + si-neg. [score:1]
We obtained several candidate genes for each of the miRNAs with the exception of miR-517a/c (Figure 2C). [score:1]
Given miR-517a/c activated NF-κB signaling in our screen, this is consistent with the well-established anti-apoptotic role of NF-κB [51, 52]. [score:1]
Interestingly, miR-517b was not a hit in our screen despite extensive homology to miR-517a/c (Figure 4A). [score:1]
miR-517a/c -induced apoptosis in HUVECs. [score:1]
Surprisingly, we observed extensive cell death in an immortalized cell line, HEK293, and an osteosarcoma cell line, U-2 OS, transfected with miR-517a/c (Figure 6A). [score:1]
These differences were likely due to a single nucleotide shift in the miR-517b mature sequence relative to miR-517a/c (Figure 4A). [score:1]
We transfected primary HUVECs with miR-517a/c and, similar to HEK293 and U2-OS cells, we observed increased cell death and CASP-3/7 activity (see Additional file 2, Figure S5). [score:1]
There are currently no reported phenotypes associated with rs72558377, but future studies may shed light on the potential consequence of this SNP and the broader biological function of miR-517a/c. [score:1]
To test if TNIP1 was indeed a functional target of miR-517a/c, we measured its protein levels in HEK293 cells transfected with the miRNA mimics. [score:1]
Our study suggests that miRNAs are common components of NF-κB signaling and miR-517a/c may play an important role in linking NF-κB signaling with cell survival through TNIP1. [score:1]
miR-517a/c were potent activators in our -TNF screen and were not hits in our +TNF screen (Table 1). [score:1]
To confirm that the effects of miR-517a/c on NF-κB signaling were not restricted to HEK293 cells, we also tested primary human umbilical vein endothelial cells (HUVECs). [score:1]
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2
[+] score: 46
Eight targets resulted significantly downregulated after treatment with 5′-AZA: CDK6 and DNMT3B (validated targets of miR-29a-3p), E2F3 (validated target of miR-34b-3p), and OLFM3 and IFNAR1 (predicted targets of miR-517a-3p) were downregulated in both cell lines. [score:15]
In silico analysis of DE miRNAs targets allowed to select four validated targets for both miR-29a-3p (CDK6, DNMT3A, DNMT3B, RAN) and miR-181c-5p (BCL2, GATA6, KIT, SIRT); five validated targets for miR-34b-3p (BCL2, CCNE2, CDK4, E2F3, MYB); four predicted targets for miR-517a-3p (IFNAR1, OLFM3, TNIP1, WEE1) (Supplementary Table S4). [score:9]
Data on the expression of miR-517a-3p are not available due to the absence of the gene encoding this miRNA in the mouse genome. [score:3]
In conclusion, our experimental data demonstrate that miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p are involved in neuroblastoma and are potential new therapeutic targets in neuroblastoma. [score:3]
Expression of miR-181c-5p and miR-517a-3p is known to be reactivated by 5′-AZA in gastric and bladder cancer, respectively [28, 29]. [score:3]
No links between miR-517a-3p and neuroblastoma have been published to date, notwithstanding it has been proposed as a tumor suppressor in several cancers [30, 31]. [score:3]
Expression profiling of 754 miRNAs, combined with methylation assays of specific CpG islands and in silico analyses, allowed us to focus on miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p. [score:2]
MiR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p regulate neuroblastoma cell viability. [score:2]
The promoter of the genes encoding seven of them (miR-29a-3p, miR-34a, miR-126, miR-141, miR-181c-5p, miR-202 and miR-517a-3p) contained CpG islands, whose methylation significantly decreased after treatment with 5′-AZA (see later). [score:1]
The more pronounced decrease of cell viability was observed in SH-SY5Y, 48h after transfection with miR-517a-3p mimics (Figure 3). [score:1]
Briefly, 1.2 x 10 [4] cells / well were reverse -transfected with miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p mimics or equal amounts of scrambled molecules and were grown for 24h and 48h. [score:1]
We focused our analysis on 12 miRNAs (miR-22, miR-29a-3p, miR-34a, miR-126, miR-140-3p, miR-141, miR-181c-5p, miR-202, miR-455-5p, miR-508-3p, miR-517a-3p and miR-576-3p). [score:1]
Cells were transiently reverse -transfected with 30 pmoles of miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p mimics or equal amounts of scrambled molecules for 24h and 48h, by using siPORTNeoFX Transfection Agent (Ambion [®], Austin, TX), according to the manufacturer's instruction. [score:1]
Transfection with miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p mimics determined a significant decrease of cell viability, both in SK-N-BE(2)-C and in SH-SY5Y. [score:1]
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3
[+] score: 22
Briefly, by using three different prediction algorithms, as well as the TarBase database for experimentally validated miRNA targets, we identified putative target genes for the miRNAs mir-517a, mir-517c and mir-519a (Fig.   5). [score:5]
Following miRNA array analysis, four miRNAs were selected based on changes in expression; mir-517c, mir-517a, mir-519a and mir-210. [score:3]
Of special interest were the three C19MC miRNAs mir-517c, mir-517a and mir-519a, which were expressed in a majority of the samples but not in the controls, i. e. untreated cells. [score:3]
org) [57], we identified potential miRNA target genes for the C19MC miRNAs mir-517a, mir-517c and mir-519a. [score:3]
FLT1 was chosen due to its significance in PE research as well as being a validated target for mir-517a/b and mir-517c [59]. [score:3]
By combining the gene lists from the three prediction algorithms, we found 33 genes for mir-517a and mir-517c as well as 872 genes for mir-519a. [score:1]
Tarbase provided one (1) experimentally supported gene for mir-517a, no genes for mir-517c and four (4) genes for mir-519a. [score:1]
After treatment with normal STBEVs, the levels of mir-517a, mir-517c and mir-519a increased significantly (p = 0.00164, p = 0.0002 and p = 0.00164 respectively). [score:1]
Based on the array results, four miRNAs (mir-517a, mir-517c, mir-519a and mir-210) were selected for further analysis using RTqPCR. [score:1]
The three placental C19MC miRNAs, mir-517a (a), mir-517c (b) and mir-519a (c), were analysed using RTqPCR. [score:1]
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4
[+] score: 20
Irrespective of p53 status, after radiation miR-302a and miR-302c up-regulated, and miR-518f down-regulated in the all cell lines, whereas after SN38 treatment up-regulated miRNAs were miR-133a, miR-155-3p, miR-204, miR-22, miR-512-3p, miR-517a, miR-517c and miR-708 in the all cell lines (Figure 3, Table 1a). [score:10]
Irrespective of wild type or mutated or null p53, after radiation treatment, miR-302a and miR-302c up-regulated, and miR-518f down-regulated in colon cancer cells, whereas after SN38 treatment up-regulated miRNAs were miR-133a, miR-155, miR-204, miR-22, miR-512-3p, miR-517a, miR-517c and miR-708 in the all colon cancer cell lines. [score:10]
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5
[+] score: 14
Here, we intended to identify suitable MREs for bladder cancer specific adenovirus -mediated TRAIL expression from the miRNAs with downregulated expression in bladder cancer, including miR-1 [18- 21], miR-99a [22], miR-100 [23], miR-101 [24, 25], miR-125b [23, 26, 27], miR-133a [18, 20, 21, 23, 28- 30], miR-143 [22, 23, 31- 33], miR-145 [21, 23, 29- 31, 34], miR-195-5p [35], miR-199a-3p [36], miR-200 [37, 38], miR-203 [39, 40], miR-205 [37], miR-218 [21, 41], miR-490-5p [42], miR-493 [43], miR-517a [44], miR-574-3p [45], miR-1826 [46] and let-7c [42]. [score:8]
The involved MREs sequences in our study were described in detail in Table  1. Table 1 MiRNA response elements (MREs) for bladder cancer-specific downregulated miRNAs miRNA primer sequences miR-1Forward: 5′-TCGAGACAAACACC ACATTCCAACAAACACC ACATTCCAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TGGAATGTGGTGTTTGT TGGAATGTGGTGTTTGTC-3′ miR-99aForward: 5′-TCGAGACAAACACC TACGGGTACAAACACC TACGGGTACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT ACCCGTAGGTGTTTGT ACCCGTAGGTGTTTGTC-3′ miR-101Forward: 5′-TCGAGACAAACACC GTACTGTACAAACACC GTACTGTACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT ACAGTACGGTGTTTGT ACAGTACGGTGTTTGTC-3′ miR-133Forward: 5′-TCGAGACAAACACC GGACCAAAACAAACACC GGACCAAAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TTTGGTCCGGTGTTTGT TTTGGTCCGGTGTTTGTC-3′ miR-218Forward: 5′-TCGAGACAAACACC AAGCACAAACAAACACC AAGCACAAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TTGTGCTTGGTGTTTGT TTGTGCTTGGTGTTTGTC-3′ miR-490-5pForward: 5′-TCGAGACAAACACC ATCCATGACAAACACC ATCCATGACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT CATGGATGGTGTTTGT CATGGATGGTGTTTGTC-3′ miR-493Forward: 5′-TCGAGACAAACACC ACCTTCAACAAACACC ACCTTCAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TGAAGGTGGTGTTTGT TGAAGGTGGTGTTTGTC-3′ miR-517aForward: 5′-TCGAGACAAACACC TGCACGAACAAACACC TGCACGAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TCGTGCAGGTGTTTGT TCGTGCAGGTGTTTGTC-3′The underscored sequences indicated MREs of miR-1, miR-99a, miR-101, miR-133 and miR-218, miR-490-5p, miR-493 and miR-517a. [score:3]
The involved MREs sequences in our study were described in detail in Table  1. Table 1 MiRNA response elements (MREs) for bladder cancer-specific downregulated miRNAs miRNA primer sequences miR-1Forward: 5′-TCGAGACAAACACC ACATTCCAACAAACACC ACATTCCAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TGGAATGTGGTGTTTGT TGGAATGTGGTGTTTGTC-3′ miR-99aForward: 5′-TCGAGACAAACACC TACGGGTACAAACACC TACGGGTACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT ACCCGTAGGTGTTTGT ACCCGTAGGTGTTTGTC-3′ miR-101Forward: 5′-TCGAGACAAACACC GTACTGTACAAACACC GTACTGTACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT ACAGTACGGTGTTTGT ACAGTACGGTGTTTGTC-3′ miR-133Forward: 5′-TCGAGACAAACACC GGACCAAAACAAACACC GGACCAAAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TTTGGTCCGGTGTTTGT TTTGGTCCGGTGTTTGTC-3′ miR-218Forward: 5′-TCGAGACAAACACC AAGCACAAACAAACACC AAGCACAAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TTGTGCTTGGTGTTTGT TTGTGCTTGGTGTTTGTC-3′ miR-490-5pForward: 5′-TCGAGACAAACACC ATCCATGACAAACACC ATCCATGACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT CATGGATGGTGTTTGT CATGGATGGTGTTTGTC-3′ miR-493Forward: 5′-TCGAGACAAACACC ACCTTCAACAAACACC ACCTTCAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TGAAGGTGGTGTTTGT TGAAGGTGGTGTTTGTC-3′ miR-517aForward: 5′-TCGAGACAAACACC TGCACGAACAAACACC TGCACGAACAAACACCGC-3′Reverse: 5′-GGCCGCGGTGTTTGT TCGTGCAGGTGTTTGT TCGTGCAGGTGTTTGTC-3′The underscored sequences indicated MREs of miR-1, miR-99a, miR-101, miR-133 and miR-218, miR-490-5p, miR-493 and miR-517a. [score:3]
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6
[+] score: 14
miR-517a/b, miR-517c, and miR-519d could suppress trophoblast cell migration and invasion by targeting a number of migration-related transcripts including CXCL6, FOXL2, NR4A2, and by upregulating the expression of sFlt-1 (7– 9). [score:10]
Placental expression of miR-517a/b and miR-517c contributes to trophoblast dysfunction and preeclampsia. [score:3]
Severe miRNAs have been identified to be responsive for hypoxia, such as miR-210, miR-517a/b, miR-424, miR-365, etc. [score:1]
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7
[+] score: 13
Eisenberg et al. also showed that miR-517* was up-regulated only in adult FSHD1 biopsies and not in any of the 9 other neuromuscular diseases studied by these authors, suggesting that this microRNA might be a potent biomarker for FSHD [51]. [score:6]
However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. [score:5]
We did not observed any miRNAs only detected in control samples but we identified 8 miRNAs which were only expressed in FSHD samples as compared to age-matched controls: miR-330, miR-331–5p, miR-34a, miR-380–3p, miR-516b, miR-582–5p, miR-517* and miR-625. [score:2]
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8
[+] score: 13
Three miRNAs were down regulated in the 10K STBMs after Hb treatment; mir-517a, mir-141 and mir-517b. [score:2]
Mir-517a, mir-141 and mir-517b were down regulated after Hb perfusion in the 10K STBMs. [score:2]
Mir-517a, mir-517b and mir-518b were chosen because of their placenta specificity [36] and mir-518b being dys-regulated in PE [41]. [score:2]
After Hb perfusion, mir-517a (p = 0.03671), mir-141 (p = 0.01219) and mir-517b (p = 0.03671) were significantly down regulated in 10K STBMs (Figure 3). [score:2]
Mir-517a and mir-517b belong to the C19MC cluster [32]. [score:1]
In the 10K STBMs mir-517a, mir-141 and mir -517b were significantly down regulated in Hb perfusions compared to controls. [score:1]
All miRNAs (mir-517a, mir-517b, mir-518b, mir-205, mir-210, mir-222, mir-141, mir-16 and mir-424) analysed in this study were present in both 10K and 150K STBMs. [score:1]
To confirm that the differences obtained between the groups were dependent on Hb perfusion, mir-141 and mir-517a were also analysed in phase I, before addition of Hb. [score:1]
Of particular interest is the alteration of two placenta specific micro -RNAs; mir-517a and mir-517b. [score:1]
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9
[+] score: 13
Akin to the results obtained for the other members of that cluster high expression was noted only in the same four cell lines with 19q13 rearrangements expressing miR-512-5p, miR-517a, and miR-519a (Figure 3a) whereas a significantly lower expression was seen in the remaining cell lines (p = 0.001659; for details see Table 2). [score:7]
To evaluate the role of either of the two miRNA clusters located in close proximity to the breakpoint region as possible targets of the 19q13 translocations in thyroid adenomas, we have first used to compare the expression of three members of the C19MC cluster, i. e. miR-512-5p, miR-517a, and miR-519a in five cell lines established from thyroid adenomas with 19q13 rearrangements and three cell lines from adenomas with other clonal abnormalities (Table 1). [score:3]
Expression analysis of miR-517a by. [score:3]
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10
[+] score: 12
Other miRNAs from this paper: hsa-mir-21, hsa-mir-323a, hsa-mir-518b, hsa-mir-323b
Interestingly, the representative placenta-specific C19MC miRNAs miR-518b and miR-517a were only clearly expressed in CP-MSCs and CV-MSCs, and barely expressed in DB-MSCs (p < 0.001 vs. [score:5]
In contrast, the placenta-specific C19MC miRNAs (miR-518b and miR517a) were only clearly detected in CP-MSCs and CV-MSCs, with low or absent expression in DB-MSCs, WJ-MSCs, and UCB-MSCs. [score:3]
Similarly, MSCs primarily expanded from umbilical cord blood (UCB-MSCs) and Wharton’s jelly tissue (WJ-MSCs) both expressed miR-323-3p (Fig. 3b) but not miR-518b and miR-517a (Fig. 3c,d). [score:3]
P8) (Fig. 5a), while levels of miR-518b and miR-517a remained relatively stable during ex vivo expansion (Fig. 5b,c). [score:1]
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11
[+] score: 10
The enriched GO categories for the downregulated targets identified for some of the individual upregulated miRNAs were as follows: Cell Homeostasis and Peroxisome for miR-34a; Cell Cycle and DNA Damage for miR-181b; and Vesicle Processes for miR-517*. [score:9]
Represented GO categories were also associated with miRNAs, such as: Cell Cycle with miR-200a and DNA Damage with miR-517*. [score:1]
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12
[+] score: 9
For example, Jin et al. recently reported that miR-517a-3p promotes lung cancer cell proliferation and invasion by targeting FOXJ3 expression [23]. [score:5]
Our data in the present study are consistent with the above findings showing the upregulation of miR-517, miR-92a, miR-127, and miR-181a in Exo [Hypoxic]. [score:4]
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13
[+] score: 9
MicroRNAs similarly expressed in both AD-affected brain and PBMC are identified (Table 2; Fig. 1), including the up-regulation of miR-34a, miR-200a and miR-520h, as well as the up-regulation let-7f, miR-371 and miR-517/517* observed in the CSF and PBMC of AD patients. [score:9]
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14
[+] score: 8
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-mir-22
However, among the three newly identified miRNAs that have transcriptional activity and are co-expressed with Alu elements, only AluJo-576611 and AluJo-135090 contain the classic B box, and AluJb-641 has no B box; neither has the upstream AluSg/x-1110454, which has been shown to be able to transcribe miR-517a. [score:3]
Multiple sequence comparisons among three Alus used in this study and AluSg/x-1110454, which resides upstream of miR-517a, revealed that the sequence GAGGCTGAGG was very highly conserved (Figure 4A). [score:1]
Recently, studies on miRNA transcription by two different groups have indicated that Pol-II or Pol-III is associated with miR-517a transcription [14, 34]. [score:1]
Of the 60 Alu-related sequences, only one is a known miRNA, miR-517a. [score:1]
A final total of 24 Alu-related miRNAs were confirmed, including the known miR-517a (Table 1). [score:1]
We not only predicted 60 Alu-related miRNAs that might be transcribed through Alu, including the previously reported miR-517a, but also identified 23 of them by Solexa sequencing. [score:1]
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15
[+] score: 8
We previously demonstrated that several down-regulated miRNAs, such as miR-1, miR-133a, miR-145, miR-218 and miR-517a, have tumor suppressive function by targeting oncogenes. [score:8]
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16
[+] score: 8
Other miRNAs from this paper: hsa-mir-486-1, mmu-mir-486a, mmu-mir-486b, hsa-mir-486-2
Studies have shown that TNIP1 is a direct functional target of miR-517a/c [43], and the overexpression of miR-486 repressed the expression level of TNIP1 in vitro [44]. [score:8]
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17
[+] score: 7
Other miRNAs from this paper: hsa-mir-93, hsa-mir-155
Three expression constructs incorporating an endogenous human microRNA Alu promoter were created by cloning the endogenous miR-517a genomic locus and then replacing the miR-517a hairpin with the miR-93, miR-155 and shLacZ hairpins (pAL-93, pAL-155, and pAL-1 respectively)(Figure 2A), as described [32]. [score:3]
"pAL" refers to the human miR-517a Alu promoter. [score:1]
In pALs-155 and -93, the pre-miR-155 and -93 hairpins replace the miR-517a hairpin respectively. [score:1]
In pAL-1, shLacZ replaces the miR-517a hairpin. [score:1]
5'Alu corresponds to a genomic fragment containing the miR-517a upstream Alu promoter [32]. [score:1]
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[+] score: 7
Similarly, Hromadnikova et al. [17] detected a downregulation of 6 miRNAs (miR-517-5p, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, and miR-525) in placental tissues of 36 FGR pregnancies: compared to the previous studies, these results seem more robust since that authors investigated more types of miRNAs and used those that were previously demonstrated to be exclusively expressed or highly expressed in placental tissues. [score:5]
In a small-scale analysis, others found that a group of miRNAs that are altered by hypoxia in trophoblasts (miR-27a, miR-30d, miR-141, miR-200c, miR-424, miR-205 and miR-451, miR-491, miR-517a, miR-518b, miR-518e, and miR-524) is elevated in FGR pregnancies (n = 14 FGR versus n = 14 controls) [47]. [score:1]
A significant elevation of several extracellular placenta-specific miRNA levels was recently showed (miR-516-5p, miR-517, miR-518b, miR-520a, miR-520h, miR-525, and miR-526a,) during early gestation in 7 pregnancies with later onset of preeclampsia and/or FGR [44]. [score:1]
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19
[+] score: 7
One miRNA, miR-517* was reported to be uniquely up-regulated in FSHD. [score:4]
While miR-517* was examined in our study, the expression was not detectable in either the FSHD and control myoblasts. [score:3]
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[+] score: 7
Other miRNAs from this paper: hsa-mir-210, hsa-mir-526b, hsa-mir-518b, hsa-mir-455
Further validating the quality of our samples, we detected miR526B, miR518B, and miR517A, three representative miRNAs encoded in the placenta-specific C19MC, as well as miR210, an miRNA shown previously to be upregulated in placenta from PE patients 26, 27, 28 (Figure 2c). [score:4]
Comparison of miRNA abundance in samples from the two patient groups showed no significant differences in miR526B, miR518B, or miR517A, demonstrating that expression of the C19MC was not notably affected in PE patients (Figure 2d). [score:3]
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21
[+] score: 7
For example, mir-202, mir-17-3p, mir-517 targets are highly expressed in EMT tumors and lowly expressed in the more luminal tumors. [score:7]
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22
[+] score: 6
Other miRNAs from this paper: hsa-mir-451a, hsa-mir-517b, hsa-mir-451b
For miR-517a and miR-517b, despite the fact that we observed their higher expression in placenta samples, both presented very low or undetectable expression in all the human normal tissues evaluated (data not shown). [score:3]
Among the top-five most highly expressed miRNAs in normal human placenta, we evaluate the expression of miR-451, miR-517a, miR-517b and miR-720 in normal human placenta samples, several normal human tissues and different cancer cell lines using RT-qPCR. [score:3]
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23
[+] 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-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-139, 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-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-190a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-429, hsa-mir-491, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, hsa-mir-500a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-637, hsa-mir-151b, hsa-mir-298, hsa-mir-190b, hsa-mir-374b, hsa-mir-500b, hsa-mir-374c, hsa-mir-219b, hsa-mir-203b
In HCC has been reported up -expression of miR-21, miR-221, miR-22, miR-15, miR-517a, and down -expression of miR-122, miR-29 family, miR-26a, miR-124, let-7 family members, and miR-199a/b-3p (Szabo et al., 2012). [score:5]
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24
[+] 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-18a, hsa-mir-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-124-3, mmu-mir-126a, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-146a, mmu-mir-200b, mmu-mir-203, mmu-mir-204, mmu-mir-205, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-203a, hsa-mir-204, hsa-mir-205, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-146a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-148a, 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-18a, mmu-mir-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-10a, mmu-mir-100, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-375, mmu-mir-375, hsa-mir-335, mmu-mir-335, mmu-mir-133a-2, hsa-mir-424, hsa-mir-193b, hsa-mir-512-1, hsa-mir-512-2, hsa-mir-515-1, hsa-mir-515-2, hsa-mir-518f, hsa-mir-518b, hsa-mir-519d, hsa-mir-516b-2, hsa-mir-516b-1, hsa-mir-517c, hsa-mir-519a-1, hsa-mir-516a-1, hsa-mir-516a-2, hsa-mir-519a-2, hsa-mir-503, mmu-mir-503, hsa-mir-642a, mmu-mir-190b, mmu-mir-193b, hsa-mir-190b, mmu-mir-1b, hsa-mir-203b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-126b, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
Significant expression of miRNAs within this cluster (miR-512-3p, miR-512-5p, mir-515-5p, miR-516b, miR-517a, miR-517c, miR-518b, miR-518f, miR-519a and miR-519d) was observed in the MaSC/basal population (Fig.   3b), whereas no highly expressed luminal-specific primate miRNAs were identified. [score:5]
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25
[+] score: 4
The deregulation of miR-517a and miR-517c promotes HCC cell proliferation via targeting Pyk2 [26]. [score:4]
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26
[+] score: 4
Hromadnikova et al. reported an upregulation of circulating C19MC miRNAs (miR-516-5p, miR-517*, miR-520a*, miR-525, and miR526a) in patients with PE (33). [score:4]
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27
[+] score: 4
In another study conducted in 2015 by Nagasaki University Graduate School of Biomedical Sciences in Japan, the researchers discovered that plasma concentration of cell-free pregnancy associated miRNAs—miR-323-3p, miR-515-3p, miR-517a, miR-517c, miR-518b—and the concentration of hCG have significant statistical differences in women with SA, EP and normal pregnancies (NP). [score:1]
Serum miR-323-3p concentrations determined by real-time PCR were significantly elevated in EP and revealed more promising results than miR-517a, miR-519d, and miR-525-3p, with a 37% sensitivity rate (at a fixed-specificity of 90%) when used as a single marker. [score:1]
Plasma cell-free concentration of miR-517a could distinguish ectopic pregnancy/ spontaneous abortion from natural pregnancy with a yield below the ROC curve of 0.9654 (95% coefficient interval 0.9172–1.0). [score:1]
Moreover, there was no significant statistical difference of cell-free serum concentration of miR-21 between three groups and they reported no relationship between serum levels of hCG and plasma cell free of miR-323-3p, miR-515-3p, miR-517a, miR-517c, miR-518b, and miR-21. [score:1]
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28
[+] score: 3
Other previously identified miRNAs are a chromosome 19 microRNA cluster (C19MC) including miR-517a, miR-519b, miR-520b, miR-520b, and miR-521, which were found to be highly expressed in human stem cells [10]; the miR-290 cluster was only detected at high levels in mouse stem cells [11]. [score:3]
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29
[+] score: 3
Furthermore, a recent study showed that miR-517a-3p accelerates lung cancer cell proliferation, migration and invasion through inhibition of FOXJ3 [174, 175]. [score:3]
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30
[+] score: 3
In comparison, soft tissue tumors and non-neoplastic muscle tissues showed uniformly higher level expression of miR-517a and miR-517b (highlighted in red in Figure 1). [score:3]
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31
[+] score: 3
Human exosomal placenta -associated miR-517a-3p modulates the expression of PRKG1 mRNA in Jurkat cells. [score:3]
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32
[+] score: 2
miR-517a performs a carcinogenic role in proliferation-related tumour subtypes and can promote the formation and development of subtype tumour. [score:2]
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33
[+] score: 1
Besides these 9 miRNAs, we also identified 12 more miRNAs in this cluster; they were miR-515-5p, miR-517a, miR-517b, miR-517c, miR-519e, miR-520b, miR-520d, miR-520f, miR-520h, miR-521, miR-525-3p, and miR-526b*. [score:1]
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