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9 publications mentioning dme-mir-190

Open access articles that are associated with the species Drosophila melanogaster and mention the gene name mir-190. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 350
Overexpression of miR-190 with a btl-Gal4 driver in mild hypoxia enhanced expression of the HRE-LacZ reporter (Fig 2) in comparison with control individuals expressing an unrelated RNAi (Fig 4A); co -expression of this miRNA along with sima RNAi suppressed this enhancement (Fig 4A). [score:11]
miR-190 directly targets and downregulates the prolyl hydroxylase fatigaThe results described so far demonstrate that miR-190 positively regulates Sima. [score:8]
In this study, we have shown that miR-190 directly targets and downregulates the oxygen sensor fatiga, thereby exerting positive regulation on the hypoxia master transcription factor Sima (Fig 8). [score:8]
Finally, we found that miR-190 directly targets the HIF prolyl hydroxylase fatiga transcript on its 3’UTR, thereby inhibiting its expression. [score:8]
While expression of the control miRNA (miR-970) did not induce changes in GFP-ODD reporter levels, expression of miR-190 resulted in increased GFP signal in the posterior compartment of the discs (Fig 6A–6H), indicating a stabilization of the GFP-ODD reporter, and suggesting downregulation of Fatiga. [score:8]
Ubiquitous overexpression of miR-190 with an actin-Gal4 (act-Gal4) driver in embryos maintained in normoxia or exposed to mild hypoxia (11% O [2]) for 4 h induced upregulation of fgaB and hsf transcripts in comparison to control embryos carrying only the act-Gal4 driver or overexpressing a control miRNA (Fig 5A and 5B). [score:8]
Collectively, these data demonstrate that miR-190 directly targets and downregulates fatiga. [score:7]
miR-190 directly targets and downregulates the prolyl hydroxylase fatiga. [score:7]
Overexpression of miR-190 inhibited fatiga luciferase reporter expression, but had no effect on the reporter in which the 3’UTR of fatiga was mutagenized. [score:7]
The screen was carried out in triplicate; overexpression of most miRNAs had no effect on HRE-LacZ reporter expression (Fig 2A and 2B), but 4 out of the 93 tested miRNAs, namely miR-190 (Fig 2C and 2G), miR-274 (Fig 2D and 2G), miR-280 (Fig 2E and 2G) and miR-985 (Fig 2F and 2G), scored as positives in the screen, inducing expression of the reporter. [score:7]
To identify direct targets of miR-190, we searched for target genes related to HIF -dependent response to hypoxia using publicly available database. [score:6]
We confirmed these results in Drosophila S2R+ cells, where overexpression of miR-190 also resulted in upregulation of both fgaB and hsf mRNAs, in comparison with cells transfected with the empty vector (S2 Fig). [score:6]
miR-190 directly targets and represses the expression of Kcnq5, a member of the voltage-gated K [+] channel family, resulting in augmented vasoconstriction of the pulmonary artery, a hallmark of hypoxic PAH [101]. [score:6]
In line with this possibility, miR-190 directly inhibits the PH domain leucine-rich repeat protein phosphatase (PHLPP), a tumor suppressor protein that inactivates the kinase AKT through Ser437 dephosphorylation [95– 97]. [score:6]
miR-190 is a positive regulator of the hypoxic response by targeting directly fatiga, which is in turn the principal negative regulator of Sima and the response to hypoxia. [score:6]
1006073.g005 Fig 5Transcript levels of two endogenous Sima target genes, fatiga B (fgaB) and heat shock factor (hsf), were analyzed by real time RT-PCR following overexpression of miR-190 or in miR-190 [KO] embryos. [score:5]
Transcript levels of two endogenous Sima target genes, fatiga B (fgaB) and heat shock factor (hsf), were analyzed by real time RT-PCR following overexpression of miR-190 or in miR-190 [KO] embryos. [score:5]
sima knock-down did not affect miR-190 hypoxic induction, suggesting that upregulation of miR-190 in hypoxia is independent of Sima (Fig 7A). [score:5]
Having analyzed HRE-LacZ reporter induction upon miR-190 loss- and gain-of-function, we studied if miR-190 affects the expression of endogenous Sima target genes. [score:5]
We propose that miR-190 positively regulates Sima -dependent transcription by inhibiting the oxygen sensor Fatiga, which is the main negative regulator of the hypoxic response. [score:5]
Since our results suggested that miR-190 is a positive regulator of Sima (Fig 2), we tested whether overexpression of miR-190 can also induce similar developmental phenotypes, and to what extent they depend on Sima activity. [score:5]
miR-190 overexpression enhances induction of Sima endogenous target genes in cell culture in normoxia. [score:5]
To determine whether miR-190 can regulate fatiga expression, we used a transgenic reporter construct that directly responds to Fatiga activity. [score:5]
Embryos ubiquitously overexpressing miR-190 under the control of an actin-Gal4 driver, were either kept in normoxia or exposed to mild hypoxia (11% O [2]) for 4 h. miR-190 overexpression did not affect sima transcript levels as compared to control embryos bearing the act-Gal4 driver only, as assessed by real time RT-PCR. [score:4]
Next, we examined whether hypoxic induction of the HIF target genes fgaB and hsf is affected in miR-190 knock-out (miR-190 [KO]) homozygous embryos or in embryos heterozygous for miR-190 [KO] and the rhea [79a] micro deletion that covers the rhea locus [40]; miR-190 is encoded in an intron of the rhea gene [33, 34] (S3 Fig). [score:4]
Sima knock-down (en-Gal4/UAS-miR-190; UAS-sima [RNAi]), or overexpression of the isoform B of Fatiga (en-Gal4/UAS-miR-190; UAS-FgaB), rescued viability, as assessed by emergence of the adults from the puparium. [score:4]
Given that miR-190 is upregulated in diverse cancer types, our findings open the possibility that miR-190 contributes to HIFα stabilization in cancer cells, thereby enhancing tumor progression. [score:4]
Knock-down of sima by RNAi completely rescued the lethality caused by miR-190 overexpression, suggesting that lethality was indeed due to Sima accumulation (Fig 3A). [score:4]
Interestingly, mammalian miR-190 is upregulated in different types of cancer, including hepatocellular carcinoma [73, 74], primary myelofibrosis [75], pancreatic [76], breast [77– 79], rectal [80] and papillary thyroid cancer [81]. [score:4]
Under low oxygen levels Fatiga activity is reduced, while miR-190 is upregulated. [score:4]
The mechanism of action of miR-190 involves the inhibition of the Drosophila PHD, thereby positively regulating HIF -dependent responses to hypoxia at the molecular and organismal level. [score:4]
Similarly to miR-190, rhea was upregulated in hypoxia in a Sima-independent manner (Fig 7C). [score:4]
To investigate whether fatiga is a direct target of miR-190, we analyzed the expression of a luciferase reporter in which the firefly luciferase coding sequence is fused to the 3’UTR of fatiga (Fig 6I). [score:4]
1006073.g006 Fig 6 fatiga is a miR-190 direct target. [score:4]
fatiga is a miR-190 direct target. [score:4]
These results suggest that hypoxic upregulation of miR-190 occurs at a transcriptional level, in a Sima-independent manner. [score:4]
Embryos were either kept in normoxia or exposed to mild hypoxia (8–11% O [2]) during 4 h. (A-B) miR-190 or miR-970 (negative control) were overexpressed ubiquitously using an act-Gal4 driver. [score:3]
Embryos were exposed to 5% O [2] for 4 h or maintained in normoxia, and expression of (A) miR-190, (B) pre-miR-190, (C) rhea and (D) fgaB transcript levels were assessed by real time RT-PCR. [score:3]
miR-190 overexpression causes lethality and enhances tracheal terminal branching in a Sima -dependent manner. [score:3]
Noteworthy, this induction was suppressed in miR-190 [KO] mutants (Fig 4B), confirming that miR-190 contributes to Sima -dependent transcription. [score:3]
These results indicate that overexpression of miR-190 can induce Sima -dependent tracheal terminal sprouting, a typical physiological response to hypoxia. [score:3]
As depicted in Fig 7B, pre-miR-190 expression increased in hypoxia as compared to normoxia, and this induction was again unaffected after sima knock-down. [score:3]
We found one miRNA, miR-190, that is induced in hypoxia and in turn enhances HIF -dependent biological responses, as well as the expression of HIF-inducible genes. [score:3]
Hypoxic induction of both HIF target genes was severely impaired in miR-190 loss-of-function embryos (Fig 5C and 5D), indicating that miR-190 is necessary for HIF activation. [score:3]
In fatiga homozygous mutant embryos (fga [9]), induction of the reporter occurs (Figs 1A and 4B; [29]), and interestingly, this expression was not altered in miR-190 [KO] homozygotes (Fig 4B), indicating that miR-190 operates upstream of the fatiga gene. [score:3]
miR-190 overexpression induces lethality and an increase of tracheal terminal sprouting in a Sima -dependent manner. [score:3]
We overexpressed miR-190 or a control miRNA with an engrailed-Gal4 driver in the posterior compartment of wing imaginal discs, and analyzed the behavior of the GFP-ODD reporter by confocal microscopy. [score:3]
miR-190 induces the expression of the HRE-LacZ reporter in a Sima -dependent manner. [score:3]
miR-190 or miR-970 (negative control) were overexpressed with an en-Gal4 driver in the wing disc posterior compartment of a line carrying the Fatiga reporter element GFP-ODD. [score:3]
Taken together, our genetic interactions data are consistent with a mo del in which miR-190 inhibits Fatiga, resulting in an enhancement of the hypoxic response. [score:3]
S2 FigmiR-190 was overexpressed in normoxic Drosophila S2R+ cells by transfection with 300 ng of a pAc-miR-190 plasmid or an empty vector as a control. [score:3]
RT-qPCR analysis revealed a significant increase of miR-190 expression in wild type embryos exposed to hypoxia (5% O [2] for 4 h), in comparison to controls maintained in normoxia (Fig 7A). [score:3]
miR-190 is induced in hypoxia, a condition in which Fatiga activity is also inhibited due to low oxygen availability (Fig 8), providing a mechanism by which miR-190 enhances the strength of the hypoxic response. [score:3]
The experiment was carried out in S2R+ cells transfected with a plasmid driving the expression of miR-190, in comparison to cells transfected with an empty vector; miR-12 and its specific luciferase reporter [31, 44] were utilized as a positive control of the system (S5 Fig). [score:3]
One of these miRNAs, miR-190, is induced in hypoxia, is necessary for Sima -dependent gene expression and promotes terminal tracheal cell sprouting. [score:3]
miR-190 enhances induction of Sima endogenous target genes. [score:3]
The pAc-miR-190 overexpression plasmid was kindly provided by M. Milán [104]. [score:3]
Overexpression of miR-190 along with Fatiga B, a highly active isoform of the oxygen sensor Fatiga [30], sharply decreased induction of the reporter (Fig 4A). [score:3]
1006073.g007 Fig 7Embryos were exposed to 5% O [2] for 4 h or maintained in normoxia, and expression of (A) miR-190, (B) pre-miR-190, (C) rhea and (D) fgaB transcript levels were assessed by real time RT-PCR. [score:3]
When overexpressed with an engrailed-Gal4 (en-Gal4) driver, miR-190, but not the control miRNA (miR-970), was associated with lethality at pupal or pharate adult stages (Fig 3A). [score:3]
miR-190 enhances transcription of endogenous Sima target genes. [score:3]
The reporter bearing the mutant binding site became insensitive to the expression of miR-190 (Fig 6J), confirming specificity of the miRNA. [score:3]
To determine if hypoxic induction of miR-190 depends on Sima, we analyzed miR-190 levels in embryos exposed to hypoxia and expressing sima RNAi. [score:3]
Overexpression of miR-190 does not affect sima mRNA levels. [score:3]
Overexpression of miR-190 (en-Gal4/UAS-miR-190 and en-Gal4/UAS-miR-190; UAS-GFP) provoked pupal lethality. [score:3]
Another bona fide miR-190 target is IGF-1, which is significantly reduced in serum of patients with hepatocellular carcinoma. [score:3]
In human bronchial epithelial cells, trivalent arsenic (A [3+]) induces the expression of miR-190, which binds the 3’UTR of PHLPP transcript, decreasing PHLPP protein levels [95, 96]. [score:3]
S4 FigOverexpression of miR-190 does not affect sima mRNA levels. [score:3]
To investigate if miR-190 upregulation in hypoxia is regulated at a transcriptional level, we evaluated the expression of pre-miR-190. [score:3]
Mo del for the regulation of the hypoxic response by miR-190. [score:2]
The results described so far demonstrate that miR-190 positively regulates Sima. [score:2]
We focused our studies on miR-190, whose occurrence in vivo has been experimentally validated by high-throughput sequencing of small RNA libraries generated from different tissues and developmental stages [33, 34]. [score:2]
org) [41– 43] predicted two potential miR-190 binding sites within the 3’ UTR of the prolyl-4-hydroxylase fatiga, the main negative regulator of Sima. [score:2]
Given that miR-190 is encoded in an intron of the rhea gene (S3 Fig), we investigated if rhea transcript levels are also upregulated in hypoxia. [score:2]
Importantly, transfection of the plasmid expressing miR-190 strongly reduced luciferase activity of the reporter containing the fatiga 3’UTR, as compared to control cells transfected with the empty vector (Fig 6J). [score:2]
Thus, it is possible that miR-190 -dependent regulation of HIF-prolyl hydroxylases is conserved in evolution. [score:2]
We next investigated if miR-190 expression is regulated by oxygen. [score:2]
No differences were detectable in sima transcript levels, either in normoxia or in mild hypoxia (S4 Fig), indicating that the miR-190 regulatory mechanism is independent of sima transcription or mRNA stability. [score:2]
Among 93 miRNAs tested, we identified miR-190, miR-274, miR-280 and miR-985 as positive regulators of Sima -dependent transcription. [score:2]
Using a ubiquitous act-Gal4 driver, we overexpressed miR-190 in embryos exposed to either normoxia or mild hypoxia (11% O [2]) for 4 h, and measured sima mRNA levels by quantitative real time RT-PCR. [score:1]
We measured mRNA levels of two well-established Sima targets by real time RT-PCR, namely fatiga B (fgaB) and heat shock factor (hsf) [30, 39] in embryos with gain- or loss-of-function of miR-190. [score:1]
Thus, miR-190 favors carcinogenesis through distinct pathways. [score:1]
Point mutations in miR-190 binding site at the fatiga 3’UTR were introduced by nested PCR with the following primers: Fw: 5’-CTGTAAATCATGAAGTATGTATATTTATGCCCTCGCTACATATTGTATG-3’; Rv: 5’-CATACAATATGTAGCGAGGGCATAAATATACATACTTCATGATTTACAG-3’. [score:1]
miR-190, pre-miR-190 and rhea were induced in hypoxia in a Sima-independent manner. [score:1]
Hypoxic induction of miR-190. [score:1]
miR-190 is induced in hypoxia in a Sima-independent manner. [score:1]
For quantification of miR-190 levels, the NCode VILO miRNA cDNA Synthesis Kit (Invitrogen, Carlsbad, CA, USA) was used, following manufacturer´s instructions. [score:1]
Sequence alignment between miR-190 and the two predicted recognition sites at the 3’UTR of fatiga are shown. [score:1]
The 2S rRNA was used for normalization in quantitative real time PCR determinations of miR-190. [score:1]
Taken together, this set of experiments suggests that miR-190 is transcriptionally induced in hypoxia, as part of the rhea transcript, in a Sima-independent manner (S3 Fig). [score:1]
The following fly stocks were from the Bloomington Drosophila Stock Center (Indiana University, Bloomington, IN, USA): w [1118], breathless-Gal4, engrailed-Gal4, dSRF-Gal4, actin-Gal4, UAS-GFP, UAS- white RNAi and miR-190 [KO]. [score:1]
Point mutations in miR-190 binding site at the fatiga 3’UTR were introduced by nested PCR with the following primers: Fw: 5’-CTGTAAATCATGAAGTATGTATATTTATGCCCTCGCTACATATTGTATG-3’; Rv: 5’-CATACAATATGTAGCGAGGGCATAAATATACATACTTCATGATTTACAG-3’. [score:1]
These results indicate that miR-190 enhances the HIF pathway, antagonizing the activity of the prolyl-4-hydroxylase Fatiga. [score:1]
To assess binding specificity of miR-190, we mutagenized the strongest miR-190 recognition site within the fatiga 3’UTR (Fig 6I). [score:1]
Intron 53 of human TLN2-001 (which is 12,893 nucleotides long) and intron 14 of rhea-RB (which is 356 nucleotides long) only share sequence similarity within the miR-190 locus [33, 34, 63– 70], reflecting the physiological relevance of this miRNA and perhaps some biological link with Rhea/Talin2. [score:1]
To analyze further these genetic interactions, we utilized miR-190 null mutant embryos (miR-190 [KO], [38]). [score:1]
To investigate if this increase of ramification depends on Sima, we coexpressed miR-190 along with a UAS- sima [RNAi], and observed complete reversion of the phenotype, attaining these larvae a normal number of TTBs (Fig 3F). [score:1]
fatiga homozygous mutants (fga [9]) exhibited induction of the reporter, which did not decrease in double homozygous miR-190 [KO], fga [9] mutants, suggesting that miR-190 operates upstream to Fatiga. [score:1]
In most mammalian species, two miR-190 family members occur, miR-190a and miR-190b. [score:1]
miR-190 enhances Sima -dependent transcription. [score:1]
To get additional evidence that miR-190 participates in the HIF pathway, we analyzed genetic interactions between miR-190, fatiga and sima, by assessing induction of the HRE-LacZ reporter as a read out. [score:1]
org), miR-190 is broadly conserved in evolution, not only within the Drosophilid lineage [34], but also in distant taxa, including mammals. [score:1]
To investigate whether miR-190 can also modulate this process, we overexpressed miR-190 under control of the tracheal terminal cell-specific driver dSRF-Gal4. [score:1]
The region encompassing exon 14 to exon 16 of rhea-RB is amplified to show that miR-190 (red) is encoded within its intron 14. [score:1]
We found that Drosophila miR-190 is induced in hypoxia. [score:1]
S3 FigSchematic representation of the rhea locus including one of its introns where miR-190 is encoded. [score:1]
Importantly, strengthening the notion of a possible involvement of miR-190 in mammalian responses to low oxygen, miR-190 is induced by hypoxia in a rat mo del of hypoxic pulmonary artery hypertension (PAH) [99– 102]. [score:1]
Remarkably, Drosophila melanogaster miR-190 is encoded in an intron of the gene rhea (S3 Fig), the homolog of talin2 (TLN2). [score:1]
Schematic representation of the rhea locus including one of its introns where miR-190 is encoded. [score:1]
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2
[+] score: 16
For expression pattern studies and hormonal treatments, we selected the three miRNAs more highly expressed (M-value between 1.6 and 5.3) in the N5 library (miR-252-3p, miR-276-5p and miR-190-5p) and the four more differentially expressed (M-value between −1.4 and −2.0) in the N6 library (bantam-3p, miR-100-5p, miR-125-5p and let-7-5p). [score:7]
In the cases of miR-276-5p, miR-190-5p, miR-252-5p and bantam-3p, there were expression bursts seen both in N5 and in N6, approximately corresponding to the peaks of 20E (Figure  2). [score:3]
Minor discrepancies, like in the case of miR-276-5p, miR-276-3p, miR-190-5p, can be due to individual variability, given that sequencing data come from a pool of nine specimens, whereas data of expression patterns is based on three particular specimens. [score:3]
These data do not correlate with quantitative sequencing data, which predicted that miR-276-5p and miR-190-5p should have shown much higher expression levels around the 20E peak of N5, whereas those of miR-252-5p and bantam-3p should have been much lower at this stage. [score:3]
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3
[+] score: 5
Other miRNAs from this paper: dme-mir-10, dme-mir-277, dme-mir-34
Further, we found that these target lists overlap (with up to 29 targets) with the well-studied miRNAs mir-34, mir-277, mir-190, and mir-10. [score:5]
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4
[+] score: 3
These included miR-SPs targeting bantam, miR-1, the K-box family (miR-2b, miR-2c and miR-13b displayed strong phenotypes; miR-2a and miR-13a were flight impaired but fell below our stringent cutoff; ), miR-7, the miR-31 family, miR-34, miR-190, miR-957, miR-986, miR-987 and miR-1001. [score:3]
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5
[+] score: 3
F F M N/A 3.39 C5152a ame-mir-190* C5152a. [score:1]
*C5152a is the reverse complement of ame-mir-190. [score:1]
Predicted mature C5152b is similar, but not identical to Drosophila dme-mir-190; C5152b is longer than dme-mir-190, and differs at only three nucleotides internally. [score:1]
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6
[+] score: 3
However, there are numerous examples of microRNAs that are present in RISC more than expected from their expression levels (miR-14-3p, miR-317-3p, 275-3p) or less than expected (miR-13a-3p, miR-317-5p, miR-190-3p). [score:3]
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7
[+] score: 1
Other miRNAs from this paper: hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, dme-mir-1, dme-mir-8, dme-mir-11, hsa-mir-34a, hsa-mir-210, dme-mir-184, dme-mir-275, dme-mir-92a, dme-mir-276a, dme-mir-277, dme-mir-33, dme-mir-281-1, dme-mir-281-2, dme-mir-34, dme-mir-276b, dme-mir-210, dme-mir-92b, dme-bantam, dme-mir-309, dme-mir-317, hsa-mir-1-2, hsa-mir-184, hsa-mir-190a, hsa-mir-1-1, hsa-mir-34b, hsa-mir-34c, aga-bantam, aga-mir-1, aga-mir-184, aga-mir-210, aga-mir-275, aga-mir-276, aga-mir-277, aga-mir-281, aga-mir-317, aga-mir-8, aga-mir-92a, aga-mir-92b, hsa-mir-92b, hsa-mir-33b, hsa-mir-190b, dme-mir-957, dme-mir-970, dme-mir-980, dme-mir-981, dme-mir-927, dme-mir-989, dme-mir-252, dme-mir-1000, aga-mir-1174, aga-mir-1175, aga-mir-34, aga-mir-989, aga-mir-11, aga-mir-981, aga-mir-1889, aga-mir-1890, aga-mir-1891, aga-mir-190, aga-mir-927, aga-mir-970, aga-mir-957, aga-mir-1000, aga-mir-309, cqu-mir-1174, cqu-mir-281-1, cqu-mir-1, cqu-mir-275, cqu-mir-957, cqu-mir-277, cqu-mir-252-1, cqu-mir-970, cqu-mir-317-1, cqu-mir-981, cqu-mir-989, cqu-mir-1175, cqu-mir-276-1, cqu-mir-276-2, cqu-mir-276-3, cqu-mir-210, cqu-mir-92, cqu-mir-190-2, cqu-mir-190-1, cqu-mir-1000, cqu-mir-11, cqu-mir-8, cqu-bantam, cqu-mir-1891, cqu-mir-184, cqu-mir-1890, cqu-mir-980, cqu-mir-33, cqu-mir-2951, cqu-mir-2941-1, cqu-mir-2941-2, cqu-mir-2952, cqu-mir-1889, cqu-mir-309, cqu-mir-252-2, cqu-mir-281-2, cqu-mir-317-2, aga-mir-2944a-1, aga-mir-2944a-2, aga-mir-2944b, aga-mir-2945, aga-mir-33, aga-mir-980
quinquefasciatus miRNAs, miR-317, miR-252, miR-276, miR-190, miR-981, and miR-2944, arise from at least two possible hairpin precursors (Table 2). [score:1]
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8
[+] score: 1
There can be two sub-categories delineated; miRNAs that do not change normally under stress, but do in dystrophic mutants (miR-92a and miR-34) and miRNAs that change as a normal response, but do not in Dys and Dg mutants (miR-956, miR-252, miR-970, miR-137, miR-986, miR-193, miR-1017, miR-962, miR-315, miR-1013, miR-980, miR-975, miR-190, miR-iab-4as-5p, miR-1003 and miR-313). [score:1]
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9
[+] score: 1
Most candidates had 5′seed sequences distinct from known miRNAs; however the following candidates, conserved with humans, were similar to those in parentheses: 5 (miR-190/190b), 19 (miR-29b-2), 92 (miR-1195), 93 (miR-134), 132 (miR-486), and 183 (miR-345-3p). [score:1]
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