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37 publications mentioning rno-mir-375

Open access articles that are associated with the species Rattus norvegicus and mention the gene name mir-375. 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: 146
Taken together, these results reveal that miR-375 targets Psen1, miR-30a targets Psen2, and miR-34a targets Notch1 by regulating the relevant 3′utr regions and repressing their translation, thereby suppressing the NICD1 level in INS-1 cells. [score:12]
Neither overexpression nor knockdown of miR-375 altered the Psen1 gene level (data not shown), whereas elevated miR-375 repressed and downregulated miR-375 enhanced PSEN1 protein level, consequently leading to the same protein expression profile for NICD1 (Fig. 3C). [score:9]
In the present study, we showed that miR-375 targets Psen1, miR-30a targets Psen2, and miR-34a targets Notch1, all of which are newly identified targets that converge onto one signaling pathway. [score:9]
The expression level of miR-375 was downregulated to 22.9%, that of miR-30a was downregulated to 28.1%, and that of miR-34a to 22.7% after anti-miRNAs transfection. [score:9]
Inhibiting miR-375, miR-30a, and miR-34a rescued glucotoxicity -induced defectsThe function of these three miRNAs was further clarified by knocking down their expression levels in INS-1 cells using miRNA inhibitors (Fig. 5A). [score:8]
Specifically, miR-375 targets Psen1, miR-30a targets Psen2, and miR-34a targets Notch1 itself, but they all decrease the NICD1 level and inactivate Notch1 signaling. [score:7]
MiR-375 targeted Psen1, miR-30a targeted Psen2, and miR-34a targeted Notch1. [score:7]
Indeed, previous research has elucidated that miR-375 regulates the expression of MTPN and PDK1 proteins 19 20, while Kim et al. have claimed that miR-30a silencing of NEUROD1 expression is an important initial event of glucotoxicity -induced beta cell dysfunction 17. [score:6]
Previously, upregulation of miR-375 and miR-30a expression by glucotoxicity has been reported in rat islets and INS-1 cells 17. [score:6]
A combination of literature screening, bioinformatics analysis, and experimental assays confirms that miR-375, miR-30a, and miR-34a regulate NICD1 protein expression via diverse targets involving γ-secretase -mediated Notch1 cleavage. [score:5]
These GK rats also showed that miR-375 and miR-30a expressions were decreased, while miR-34a expression was significantly increased (Fig. 6D). [score:5]
The combined use of bioinformatics prediction softwares (TargetScan and miRanda) and literature screening pointed to miR-375, miR-30a, and miR-34a as potential targets for further exploration. [score:5]
The alteration in this expression pattern for miR-375 is related to the transcriptional activity of PDX1, since miR-375 is one of its target genes 33. [score:5]
Protein levels were determined following overexpression or knockdown of miR-375 (C), miR-30a (F), or by miR-34a (I). [score:4]
miR-375, miR-30a, and miR-34a mimicked glucotoxicity -induced defectsThe expression of miR-375, miR-30a and miR-34a was significantly induced by high glucose in both rat pancreatic islets (Fig. 4A) and INS-1 cells (Fig. 4B). [score:3]
Effects of miR-375, miR-30a, and miR-34a expression of INS-1 cells. [score:3]
The levels of miR-375 and miR-34a were modestly elevated (Fig. 7D), in parallel with the decreased gene expression levels of components of γ-secretase and Notch1 (Fig. 7E). [score:3]
These data demonstrated that inhibition of miR-375, miR-30a, and miR-34a can partially rescue the beta cell apoptosis caused by glucotoxicity. [score:3]
In the present study, miR-375 expression increased initially but was significantly decreased by high glucose over time. [score:3]
miR-375, miR-30a and miR-34a expression levels (D). [score:3]
Inhibiting miR-375, miR-30a, and miR-34a rescued glucotoxicity -induced defects. [score:3]
The expressions of miR-375, miR-30a and miR-34a were determined after 24 h miRNA transfection (C). [score:3]
Elevated levels of miR-375, miR-30a, and miR-34a decreased the K [+]-stimulated insulin secretion index (KSI) (SEM Fig. 3A), insulin content (SEM Fig. 3B), and insulin gene expression (SEM Fig. 3B), and increased the numbers of apoptotic cells (Fig. 4D). [score:3]
The expression of miR-375, miR-30a and miR-34a was significantly induced by high glucose in both rat pancreatic islets (Fig. 4A) and INS-1 cells (Fig. 4B). [score:3]
miR-375 and miR-34a expression levels (D). [score:3]
In conclusion, we have shown that miR-375, miR-30a, and miR-34a orchestrate the regulation of γ-secretase -mediated Notch1 cleavage in a glucotoxicity setting in pancreatic beta cells. [score:2]
This study was undertaken to elucidate the regulatory networks operating between miRNAs (miR-375, miR-30a, and miR-34a) and the presenilin/Notch1 pathway in the context of glucotoxicity -induced pancreatic beta cell impairment. [score:2]
How to cite this article: Li, Y. et al. A Presenilin/Notch1 pathway regulated by miR-375, miR-30a, and miR-34a mediates glucotoxicity induced-pancreatic beta cell apoptosis. [score:2]
The miRNA mimics were introduced to enforce cellular levels of miR-375, miR-30a, and miR-34a in INS-1 cells (Fig. 4C). [score:1]
miR-375, miR-30a, and miR-34a mimicked glucotoxicity -induced defects. [score:1]
The present study and other studies have shown that elevation of miR-375, miR-30a, or miR-34a individually results in beta cell dysfunction, decreases cell survival, and increases apoptosis, thereby mimicking the cellular phenotype provoked by glucotoxicity. [score:1]
The repression of PSEN1 by high glucose was recovered by anti- miR-375, repression of PSEN2 was recovered by anti-miR-30a, and repression of NOTCH1 was recovered by anti- miR-34a; all of these responses resulted in the recovery of NICD1 protein level (Fig. 5B). [score:1]
The luciferase activity assays showed that miR-375 inhibited the activity of the wt- Psen1 construct when compared with a vector control, whereas no alteration was observed with the mt- Psen1 construct (Fig. 3B). [score:1]
Wt and mt plasmids were cotransfected with relative miRNAs for 24 h, and luciferase reporter activities were analyzed for miR-375 toward Psen1 (B), miR-30a toward Psen2 (E), and miR-34a toward Notch1 (H). [score:1]
However, Notch1 signaling is only associated with glucotoxicity -induced beta cell apoptosis and its effects are unlike those evoked by miR-375, miR-30a, and miR-34a. [score:1]
As shown in Fig. 3A,D,G, the miRNA response element (MRE) was well matched between miR-375 and Psen1, between miR-30a and Psen2, and between miR-34a and Notch1. [score:1]
Elevated serum levels of miR-375 and miR-30a are also observed in diabetic patients 31 32. [score:1]
Taken together, these results suggest that miR-375, miR-30a, and miR-34a are capable of mimicking glucotoxicity -induced beta cell impairment and NOTCH1 inactivation associated with these miRNAs -induced beta cell apoptosis. [score:1]
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2
[+] score: 120
Other miRNAs from this paper: rno-mir-7a-1, rno-mir-7a-2, rno-mir-7b, rno-mir-451
In K562 cells, up-regulated expression of microRNA-375 (miR-375) was associated with down-regulated expression of 14-3-3ζ [15]. [score:11]
Therefore, we speculated that the low expression of 14-3-3ζ might be regulated in part due to the over -expression of miR-451 and miR-375, and the over -expression of p53 may be caused by the down-regulation of 14-3-3ζ in spina bifida aperta. [score:11]
In Doxorubicin (DOX) -induced senescent K562 cells, the up-regulation of miR-375 was associated with down-regulated expression of 14-3-3ζ, indicating that 14-3-3ζ was a downstream effector of miR-375 [15]. [score:9]
These data suggest that the reduced expression of 14-3-3ζ plays a role in the excessive apoptosis that occurs in spina bifida and may be partly regulated by the over -expression of miR-451 and miR-375, and the consequent up-regulation of p53 might further promote apoptosis in spina bifida. [score:9]
Thus, we speculated that the low expression of 14-3-3ζ, which may be regulated by the over -expression of miR-451 and miR-375, and the consequent up-regulation of p53 may contribute to excessive apoptosis in spina bifida. [score:9]
Transfection of gastric cancer cells with miR-375 induces the significant down-regulation of 14-3-3ζ expression and a marked reduction in cell viability. [score:6]
We discovered that, in contrast to the reduction of 14-3-3ζ expression, the expression of miR-451, miR-375 and p53 increased in spina bifida rat fetuses. [score:5]
We found that, as compared with control fetuses, the expression of miR-375 in spina bifida was significantly up-regulated at E13, and miR-451 was increased at E13 and E15. [score:5]
These data suggest that the low expression levels of 14-3-3ζ in spina bifida aperta may be partially regulated by miR-375 and miR-451. [score:4]
To initially explore the molecular mechanisms of apoptosis in NTDs, we investigated the expression of microRNA-7 (miR-7), microRNA-375 (miR-375) and microRNA-451 (miR-451), which are known to down-regulate 14-3-3ζ in several different cell types. [score:4]
Therefore, in this paper, we confirmed the expression of 14-3-3ζ in spinal cords from normal rat fetuses and fetuses with spina bifida from E11 to E19, and selected miR-7, miR-375 and miR-451 as upstream regulators and p53 as the downstream effector of 14-3-3ζ. [score:4]
Expression of miR-7, miR-375 and miR-451 in spinal cords of rat fetuses. [score:3]
In subgroup 2, the expression of miR-7, miR-375 and miR-451 was similar to that in controls (Figure 3, A - miR-7, B - miR-375, C - miR-451). [score:3]
One-way ANOVA was used to evaluate differences in 14-3-3ζ expression (both in mRNA and protein levels), miR-7, miR-375, miR-451 and p53 protein expression among the controls, subgroup 1 and subgroup 2. If a significant P-value was reached, the SNK post-hoc test was used for pairwise comparisons to identify which means were significantly different from one another. [score:3]
0070457.g003 Figure 3Expression of miR-7 (A), miR-375 (B) and miR-451 (C) in spinal cords of control group (blue), subgroup 1 (red) and subgroup 2 (pink) embryos at E12, E13 and E15 detected by qRT-PCR. [score:3]
However, the expression of miR-7, miR-375 and miR-451 in subgroup 2 was similar to that in control fetuses. [score:3]
Further analysis showed that miR-375 targets the 3′-UTR of 14-3-3ζ [59]. [score:3]
Furthermore, we showed that, in contrast to the reduction of 14-3-3ζ expression, the levels of miR-451, miR-375 and p53 increased in spina bifida rat fetuses. [score:3]
However, in subgroup 1, the expression of miR-375 and miR-451 was significantly different from control fetuses. [score:3]
Accompanying the reduced expression of 14-3-3ζ, miR-375, miR-451 and p53 were all increased. [score:3]
To initially explore the mechanism by which 14-3-3ζ is down-regulated in spina bifida, we measured miR-7, miR-375 and miR-451 (upstream regulators of 14-3-3ζ) in normal and defective spinal cords at E12, E13 and E15. [score:3]
Expression of miR-7 (A), miR-375 (B) and miR-451 (C) in spinal cords of control group (blue), subgroup 1 (red) and subgroup 2 (pink) embryos at E12, E13 and E15 detected by qRT-PCR. [score:3]
Over -expression of miR-375 and miR-451 in Defective Spinal Cords. [score:3]
Similarly, the different expression levels of 14-3-3ζ, miR-7, miR-375, miR-451 and p53 among multiple developmental stages were also evaluated by one-way ANOVA and the SNK post-hoc test. [score:2]
Compared with controls, the expression of miR-375 was significantly increased at E13 in spina bifida fetuses (1.328±0.218 vs. [score:2]
Further investigation is necessary to determine why 14-3-3ζ is expressed at low levels at E12 in spina bifida and how 14-3-3ζ is regulated by miR-375 and miR-451 at E13 and E15. [score:2]
U6 (as the endogenous control gene), miR-7, miR-375 and miR-451 cDNA was reverse-transcribed from the total RNA (obtained from the same sample used for the mRNA expression assays) using specific primers and a TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems, USA) in accordance with the manufacturer’s instructions. [score:1]
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[+] score: 100
Figure 3Effects of formononetin on the mRNA expression of miR-375 in CNE2 cells miR-375 mRNA expression was significantly upregulated by 0.1 and 0.3 μM formononetin. [score:8]
The effects on proliferation may be attributed to the direct binding of formononetin to the ER, which then activates miR-375 and down-regulates PTEN expression. [score:7]
In combined treatment groups, cells were pre-incubated with the MAP2K1 inhibitor PD98059 or the miR-375 inhibitor for 60 min, followed by co-administration of 0.3 μM formononetin and PD98059 or the miR-375 inhibitor. [score:7]
Administration of PD98059 or the miR-375 inhibitor abolished the formononetin -mediated inhibitory effect on late apoptosis (PD98059, 4.20 ± 0.3%; miR-375 inhibitor, 4.8 ± 0.12; p < 0.05 vs. [score:7]
[*] = P < 0.05 vs control; n = 3. miR-375 mRNA expression was significantly upregulated by 0.1 and 0.3 μM formononetin. [score:6]
PD98059 and miR-375 inhibitor decreased the expression level of bcl-2 protein induced by 0.3 μM formononetin. [score:5]
Our results demonstrate that formononetin decreases the amount of late apoptotic cells and elevates bcl-2 protein expression, both of which were reversed by the addition of PD98059 and the miR-375 inhibitor. [score:5]
MAP2K1 inhibitor PD98059, miR-375 inhibitor and anti-bcl-2 antibody were purchased from Santa Cruz, CA, USA. [score:5]
This effect was reversed by the addition of either the MAP2K1 inhibitor, PD98059, or the miR-375 inhibitor (Figure 4C, 4D). [score:5]
In this study, a low concentration of formononetin decreased PTEN protein expression, in turn leading to growth of CNE2 cells, which was effectively reversed by the miR-375 inhibitor. [score:5]
Moreover, the miR-375 inhibitor reversed the decreased percentage of late apoptotic cells and the protein expression of bcl-2 caused by formononetin. [score:5]
MiR-375 inhibitor reversed the down-regulated effect. [score:5]
In this study, both ERα and miR-375 levels were up-regulated by formononetin. [score:4]
On the next day, cells were randomly divided into different groups, including control, 0.1 μM, 0.3 μM, 1 μM of formononetin, 0.3 μM formononetin + PD98059 or 0.3 μM formononetin + miR-375 inhibitor groups. [score:3]
Effects of formononetin on the mRNA expression of miR-375 in CNE2 cells. [score:3]
To evaluate ERα protein expression, cells were exposed to 0, 0.1, 0.3, or 1 μM formononetin for 48 h. To measure bcl-2 and PTEN protein expression, cells were incubated with 0.1, 0.3 and 1 μM formononetin in the presence or absence of PD98059 or the miR-375 inhibitor for 48 h. To analyze cell apoptosis, CNE2 cells were harvested and washed three times with ice-cold phosphate buffer solution (PBS). [score:3]
Formononetin increases miR-375 mRNA expression in CNE2 cells. [score:3]
In addition, PTEN appears to be an essential target of miR-375 activity in formononetin -treated cells. [score:3]
Our previous study indicated that there is positive feedback regulation between ERα and miR-375 in breast cancer MCF-7 cells [15]. [score:2]
Nevertheless, the association between miR-375 and PTEN in NPC development has not been clarified. [score:2]
Recently, miR-375 has been identified as an essential miRNA with the capacity to enhance ER signaling in cells [32]. [score:1]
To our knowledge, this is the first study to show that the ERα-miR-375-PTEN-ERK1/2-bcl-2 pathway is involved in cell proliferation. [score:1]
These findings confirmed that formononetin exerts a proliferative effect on CNE2 cells by activating miR-375. [score:1]
Our RT-PCR analysis showed that 0.1 and 0.3 μM formononetin significantly increased miR-375 mRNA levels in CNE2 cells (0.1 μM formononetin, 1.203 ± 0.054%; 0.3 μM formononetin, 1.421 ± 0.062%; control, 1 ± 0.032%; p < 0.05) (Figure 3). [score:1]
These findings imply that the proliferation of CNE2 cells induced by formononetin might be related to formononetin’s effect on miR-375-PTEN-ERK1/2-bcl-2 activation. [score:1]
Our recent report reveals a positive feedback loop between ERα and miR-375 in ER -positive breast cancer cells. [score:1]
Formononetin promotes the functional activation of ERα-miR-375. [score:1]
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4
[+] score: 68
In particular, the direct involvement of miR-375 in insulin secretion via targeting myotrophin (MTPN) expression [11, 12] and glucose homeostasis via targeting phosphoinositide -dependent protein kinase 1 (PDK-1) is well described [13, 14]. [score:8]
miR-375 is abundantly expressed in β cells and serves as a negative regulator of insulin secretion via targeting myotrophin expression [11]. [score:8]
Zhou J. Song S. Cen J. Zhu D. Li D. Zhang Z. MicroRNA-375 is downregulated in pancreatic cancer and inhibits cell proliferation in vitro Oncol. [score:5]
Recently, it has been shown that miR-375 expression is decreased in pancreatic cancer, and overexpression of miR-375 impacts cell proliferation and apoptosis in pancreatic cancer cells [30, 31]. [score:5]
Another important target of miR-375 is PDK1 in β cells, which results in a decrease of glucose regulation [13]. [score:4]
Based on previous work, the expression of the two increased miRNA species miR-375 and miR-210 and the three decreased miRNAs, miR-203, miR-185 and miR-450a, is involved in the regulation of insulin secretion and pancreatic β cell function [11, 26, 27, 28]. [score:4]
Zhou J. Song S. He S. Zhu X. Zhang Y. Yi B. Zhang B. Qin G. Li D. MicroRNA-375 targets PDK1 in pancreatic carcinoma and suppresses cell growth through the Akt signaling pathway Int. [score:4]
Latreille M. Herrmanns K. Renwick N. Tuschl T. Malecki M. T. McCarthy M. I. Owen K. R. Rulicke T. Stoffel M. miR-375 gene dosage in pancreatic β-cells: Implications for regulation of β-cell mass and biomarker development J. Mol. [score:3]
The repeated identification of miR-375 in diabetes mo dels and the apparent high expression in β cells demands a further qualification of this potential type 2 diabetes progression biomarker in animals and, potentially, human studies. [score:3]
Increased pancreatic miR-375 expression was reported in T2D patients [15] and also in animal mo dels, such as ob/ ob mice [16]. [score:3]
Therefore, both miR-29a and miR-375 could be assessed in future studies as potential translatable biomarkers. [score:3]
Li Y. Xu X. Liang Y. Liu S. Xiao H. Li F. Cheng H. Fu Z. miR-375 enhances palmitate -induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression Int. [score:3]
It needs to be determined whether miR-375 changes in plasma reflect expression changes of the miRNA in the pancreas at a constant rate of β cell death or if miR-375 reflects indeed the apoptosis of β cells. [score:3]
Furthermore, chemical induced mo dels using streptozotocin (STZ) are wi dely used as pancreas injury mo dels [24], and miR-375 has been found increased upon induction of diabetes [11]. [score:1]
Therefore, we can only hypothesize that miR-375 could reflect progressive β cell death. [score:1]
Nevertheless, a markedly increased circulating miR-375 level in response to streptozotocin, indicating acute β cell injury, was described several times [24, 29]. [score:1]
Therefore, the strong augmentation of miR-375 blood level (>8-fold) at late-stage diabetes in our study may still reflect ongoing β cell death. [score:1]
At late-stage diabetes, the circulating level of 12 miRNAs was specifically altered; the circulating level of miR-375, miR-210 and miR-133a was increased, and the circulating levels of let-7i, miR-140, miR-450a, miR-185, miR-186, miR-151-3p, miR-203, miR-16 and miR-685 were strongly diminished versus their levels at the pre-diabetes stage (Figure 4). [score:1]
Recently, it was demonstrated that circulating miR-375 levels in mice only originated in a small proportion from β cells, but mainly from various neuroendocrine cells from lung, gastrointestinal tract, thyroid and adrenals [29]. [score:1]
Altered miR-375 level does not exclusively reflect T2D pathophysiology. [score:1]
Our study revealed a continuous elevation of circulating miR-375 levels. [score:1]
Poy M. N. Hausser J. Trajkovski M. Braun M. Collins S. Rorsman P. Zavolan M. Stoffel M. miR-375 maintains normal pancreatic α- and β-cell mass Proc. [score:1]
The eight circulating miRNAs, miR-29a, miR-34a, miR-375, miR-103, miR-107, miR-132, miR-142-3p and miR-144, and the two tissue-specific miRNAs, miR-199a-3p and miR-223, were identified to be significantly altered in T2D across a meta-analysis of controlled profiling studies [51]. [score:1]
Overall, the blood level of 3 miRNA species is significantly elevated, namely miR-133a, miR-375 and miR-210. [score:1]
Apart from miR-375, none of these miRNAs were strongly and significantly changed in our study. [score:1]
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5
[+] score: 62
In humans, computational predictions show that miR-375 has two non-conserved target sites in the 3’UTR of AIFM1 mRNA (Target Scan v. 7.1 release June 2016) (Agarwal et al., 2015), and one target site in the CAV1 3’UTR identified by another miRNA target prediction program (RNA22 algorithm implemented at miRWalk 2.0) (Dweep & Gretz, 2015). [score:9]
In the rat insulin-secreting cell line, INS-1 832/13, we previously showed the reduction of Aifm1 and Cav1 mRNA expression upon miR-375 over -expression delineating the conserved targeting in rodents of these genes by miR-375 (Salunkhe et al., 2015). [score:7]
Although miR-375 is also predicted to target CAV1 3’UTR mRNA, miR-375 expression was not elevated at higher confluences, implying that CAV1 mRNA is potentially regulated by other factors. [score:6]
The negative effect of miR-375 on both the mRNA and protein levels of the two genes has been demonstrated, and in the islets of 375 KO mice, increased expression of these targets was also detected at the mRNA level (Poy et al., 2009). [score:5]
Expression of miR-375 and its targets in INS-1 832/13 cells (A–C) or in EndoC-βH1 cells (D–F). [score:5]
In INS-1 832/13 cells, we did not detect any significantly altered expression of neither miR-375 nor its targets among the different confluences (Figs. 2A– 2C). [score:5]
The genes Aifm1 and Cav1 are among the many genes shown to be directly targeted by miR-375 in mouse beta cells. [score:4]
Likewise in the human EndoC-βH1 cells, the expression of miR-375 was similar at all confluences (Fig.  3D). [score:3]
This study mainly addressed the issue whether confluence affects miR-375 expression, as it is one of the most enriched miRNAs in the pancreatic beta cells influencing diverse molecular processes, from insulin secretion to cellular growth and proliferation (Eliasson, 2017; Poy et al., 2004; Poy et al., 2009; Salunkhe et al., 2015). [score:3]
We found virtually no significant differences in the expression levels of miR-375, CAV1 mRNA and AIFM1 mRNA at higher confluences, from 60%–100%, either in the rat or human beta cell lines. [score:3]
Since its discovery, miR-375 has been shown to negatively regulate a plethora of genes involved in pancreatic beta cell function (Eliasson, 2017) such as in insulin secretion by regulating myotrophin (Mtpn) (Poy et al., 2004) and various voltage-gated sodium channels (SCNs) (Salunkhe et al., 2015). [score:3]
3503/fig-2 Figure 2(A) miR-375 expression at different cell confluence of INS-1 832/13 cells. [score:3]
Knock out of miR-375 in mouse (375 KO), resulted in hyperglycaemic animals with defective proliferative capacity of endocrine cells leading to decreased beta cell mass (Poy et al., 2009). [score:2]
Because many functional assays, e. g., insulin secretion assay, being performed on beta cell lines require optimal culture conditions including cell densities, we therefore set out to investigate whether confluence affects the expression of miR-375 and two of its validated targets in the mouse beta cell, Aifm1 and Cav1, in the rat INS-1 832/13 cells and in the human EndoC-βH1 cells. [score:1]
Although we showed that miR-375, which is one of the most enriched beta cell miRNA was not significantly influenced by confluence level in cultured rat and human beta cell lines, we clearly demonstrated that miR-132 and miR-212 are more dependent on cellular densities, as was shown for some miRNAs in other cells types (Hwang, Wentzel & Men dell, 2009; Van Rooij, 2011). [score:1]
The following primers from TaqMan [®] Gene Expression and TaqMan [®] miRNA Assays were used for qPCR: Cav1/CAV1 (Rn00755834_m1/Hs00971716_m1), Aifm1/AIFM1 (Rn00442540_m1/ Hs00377585_m1), miR-375 (TM_ 000564), miR-200a (TM_000502), miR-130a (TM_00454), miR-152 (TM_000475), miR-132 (TM_000457) and miR-212 (TM_002551) were used for qPCR. [score:1]
The first miRNA discovered in the pancreatic islet cells was miR-375 (Poy et al., 2004), which is one of the most highly-enriched miRNAs in the pancreatic islets. [score:1]
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[+] score: 41
Three general trends of miRNA expression trajectories were observed for Wistar islets at 2.8G vs 16.7G: i) increased expression as exhibited by rno-miR-132, rno-miR-212 and rno-miR-409-3p, ii) decreased expression as in the case of rno-miR-124, rno-miR-142-3p, rno-miR-375, rno-miR-335, rno-miR-130a and rno-miR-708 and, iii) no change as seen in rno-miR-376a, rno-miR-142-5p and rno-miR-433. [score:7]
Rat miR-375, miR-132 and miR-708 are indicated for reference, representing no significant change (dark tones), upregulated (yellow tones) and downregulated (blue tones) miRNAs in GK. [score:7]
0018613.g004 Figure 4Three general trends of miRNA expression trajectories were observed for Wistar islets at 2.8G vs 16.7G: i) increased expression as exhibited by rno-miR-132, rno-miR-212 and rno-miR-409-3p, ii) decreased expression as in the case of rno-miR-124, rno-miR-142-3p, rno-miR-375, rno-miR-335, rno-miR-130a and rno-miR-708 and, iii) no change as seen in rno-miR-376a, rno-miR-142-5p and rno-miR-433. [score:7]
Data analysis and presentation are as described for Figure 3. In comparison, the expression trajectories of some miRNAs in the GK islets also follow similar trends as in the Wistar islets, such as rno-miR-124, rno-miR-142-3p and rno-miR-375. [score:3]
Data analysis and presentation are as described for Figure 3. In comparison, the expression trajectories of some miRNAs in the GK islets also follow similar trends as in the Wistar islets, such as rno-miR-124, rno-miR-142-3p and rno-miR-375. [score:3]
The link between miRNA and diabetes began with the discovery of a highly-expressed pancreatic islet miRNA, miR-375. [score:3]
In general, aside from more significant changes in expression levels of miRNAs at 24 h incubation compared to 1 h incubation, three trends in terms of expression changes are also observed in the Wistar islet upon stimulation at 16.7G as compared to 2.8G: i) increasing miRNA levels, as displayed by rno-miR-132, rno-miR-212 and rno-miR-409-3p, ii) decreasing miRNA levels as exhibited by rno-miR-124, rno-miR-142-3p, rno-miR-375, rno-miR-335, rno-miR-130a and rno-miR-708, and iii) no significant change as displayed by rno-miR-376a, rno-miR-142-5p and rno-miR-433. [score:3]
Recently it was shown that miR-375 knockout mice display elevated plasma glucose levels due to a small reduction in beta cell mass with a concomitant increase in the number of alpha cells per islet as well as increased circulating glucagon [12]. [score:2]
As a negative control we included rno-miR-375, being found not to be differentially-regulated in the arrays (Figure S1B). [score:2]
In contrast, rno-miR-212 and rno-miR-132 showed the opposite trend leading to decreased miRNA levels upon stimulation at 16.7 G. Thus, for miRNAs that increases with increasing glucose concentrations in the normal Wistar islets, the GK islet miRNAs levels go down (rno-miR-132 and rno-miR-212) or do not change (rno-miR-409-3p), whereas for miRNAs whose levels decrease with increasing glucose concentration in Wistar islets, the GK islet miRNAs is also reduced (e. g. rno-miR-124, rno-miR-142-3p, rno-miR-375) (Fig. 4). [score:1]
Mir-375 was included as a non-regulated control. [score:1]
Even rno-miR-375 which was non-responsive at stimulatory conditions in Wistar significantly increased in GK at 16.7G (Fig. 3; p<0.05). [score:1]
However, despite these attempts in the GK islet to attain normal levels of miRNAs, failures were seen in most GK miRNAs wherein the levels at 16.7G either overshoot those of Wistar's as in rno-miR-142-3p, rno-miR-142-5p, rno-miR-375 and rno-miR-124, or completely miss the normal levels as in the case of rno-miR-335 and rno-miR-376a (Fig. 4). [score:1]
[1 to 20 of 13 sentences]
7
[+] score: 26
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-17, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-137, mmu-mir-140, mmu-mir-150, mmu-mir-155, mmu-mir-24-1, mmu-mir-193a, mmu-mir-194-1, mmu-mir-204, mmu-mir-205, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-143, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-222, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-143, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-150, hsa-mir-193a, hsa-mir-194-1, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-34a, rno-mir-322-1, mmu-mir-322, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-140, rno-mir-350-1, mmu-mir-350, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-33, mmu-mir-222, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-375, mmu-mir-375, mmu-mir-133b, hsa-mir-133b, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-19b-1, rno-mir-19b-2, rno-mir-23a, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-27b, rno-mir-29a, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-31a, rno-mir-32, rno-mir-33, rno-mir-34a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-106b, rno-mir-126a, rno-mir-135a, rno-mir-137, rno-mir-143, rno-mir-150, rno-mir-193a, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-204, rno-mir-205, rno-mir-222, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, mmu-mir-410, hsa-mir-329-1, hsa-mir-329-2, mmu-mir-470, hsa-mir-410, hsa-mir-486-1, hsa-mir-499a, rno-mir-133b, mmu-mir-486a, hsa-mir-33b, rno-mir-499, mmu-mir-499, mmu-mir-467d, hsa-mir-891a, hsa-mir-892a, hsa-mir-890, hsa-mir-891b, hsa-mir-888, hsa-mir-892b, rno-mir-17-2, rno-mir-410, mmu-mir-486b, rno-mir-31b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-499b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, hsa-mir-486-2, mmu-mir-126b, rno-mir-155, rno-let-7g, rno-mir-15a, rno-mir-196b-2, rno-mir-322-2, rno-mir-350-2, rno-mir-486, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
These candidate miRNAs included representatives that exhibited regulated patterns of expression from each of the two primary classes detected, namely: those with highest expression in the caput (let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p), or highest expression in the cauda (miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:8]
In order to verify the next generation sequence data, nine differentially expressed miRNAs were selected for targeted validation using qRT-PCR, including representatives with highest expression in the proximal (caput: let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p) and distal (cauda: miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:7]
0135605.g008 Fig 8In order to verify the next generation sequence data, nine differentially expressed miRNAs were selected for targeted validation using qRT-PCR, including representatives with highest expression in the proximal (caput: let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p) and distal (cauda: miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:7]
In this context, qPCR confirmed highly significant down-regulation of let-7c-5p, let-7b-5p, miR-375-3p, miR-467d-3p, and miR-200c-3p between the proximal and distal epididymal segments. [score:4]
[1 to 20 of 4 sentences]
8
[+] score: 26
Overexpression of the β-cell specific miRNA, miR-375, in pancreatic islets reduce insulin secretion [17] and reduced β-cell mass was detected in the miR-375 knock-out mouse as well as hyperglycaemia [19]. [score:4]
A. Insulin mRNA expression level is reduced in RIP-Cre Dicer1 [Δ/Δ], B. Mature miR-375 is significantly reduced while the pri-miR-375 species accumulates in the knockout. [score:4]
To verify that the knock-down of dicer effects miRNA expression we measured the expression of the β-cell specific miRNA, mir-375, and found that it was reduced by 70% in the RIP-Cre Dicer1 [Δ/Δ] compared to littermate control mice (Fig. 8 B). [score:3]
Insulin, miR-375 and pri-miR-375 expression in sorted β-cells. [score:3]
It remains unclear whether miR-375 knock-out mice develop overt diabetes. [score:2]
26 were not detected in the knockout including the most abundant islet miRNAs, miR-375 and miR-7a. [score:2]
Since our mo del is characterized by altered miRNAs processing, including miR-375, it is likely that the reduced expression of miR-375 in RIP-Cre Dicer1 [Δ/Δ] mice (Fig. 8B) contributes to diabetes development although it appears clear that other miRNAs have to be involved in the pathophysiology of these mice. [score:2]
The β-cell enriched miRNA miR-375 has been demonstrated to influence insulin mRNA levels [16] as well as the exocytotic process [17]. [score:1]
For mature miR-375, stem-loop qPCR was performed normalized against snoRNA-202 and snoRNA-412. [score:1]
This was accompanied by an accumulation of pri-miRNA-375 in the RIP-Cre Dicer1 [Δ/Δ] β-cells (Fig. 8B). [score:1]
Moreover, the level of miRNA-375, together with miRNA-127-3p and miR-184 is positively correlated to insulin mRNA levels in islets from human donors and the association between these miRNAs and β-cell function was deranged in islets from glucose intolerant donors [18]. [score:1]
Thus, a number of miRNAs, including miR-375, contribute to efficient β-cell function and protection from diabetes. [score:1]
These include the islet-specific miR-375 and another abundant islet miRNA, miR-7a [28]. [score:1]
[1 to 20 of 13 sentences]
9
[+] score: 26
miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group (Table 5). [score:7]
Ouaamari et al. found that miR-375 acts as a direct function with the 3′ untranslated region (3′UTR) of PDK1 mRNA, thus decreasing PDK1 protein, and it may impact on cell proliferation given its key role in the PI 3-kinase/PKB cascade. [score:4]
PDX-1 (3′-phosphoinositide -dependent protein kinase-1) is one of the validated target genes of miR-375. [score:3]
In gene array and real-time PCR experiment, we found that TM could increase the expression of miR-375 in islet of diabetic rats. [score:3]
Poy et al. found that inhibition of endogenous miR-375 function enhanced insulin secretion [23]. [score:3]
miR-375 is a regulator in the process of exocytosis of insulin during glucose-stimulated insulin release. [score:2]
The expression of miR-375 is decreased in diabetic Goto-Kakizaki (GK) rats, compared with Wistar rats [25]. [score:2]
In addition, mice lacking miR375 (375 KO) are hyperglycemic and exhibit increased total pancreatic alpha-cell numbers and decreased pancreatic beta-cell mass [24]. [score:1]
These actions may be through activating miR-375 and miR-30d to increase insulin secretion and action. [score:1]
[1 to 20 of 9 sentences]
10
[+] score: 22
Among the 11 significantly dysregulated miRNAs, 4 miRNAs were up-regulated (miR-34c, miR-374, miR-181a, and miR-let-7c-1), and 7 miRNAs were down-regulated (miR-1188, miR-770-5p, miR-127-5p, miR-375, miR-331, miR-873-5p, and miR-328a) (differentially expressed miRNAs were defined by a fold-change >1.5, up or down-regulated; p <0.05). [score:13]
Some of the up-regulated (miR-34c, miR-374, miR-181a, and miR-let-7c-1) and down-regulated (miR-1188, miR-770-5p, miR-127-5p, miR-375, miR-331, miR-873-5p, and miR-328a) miRNAs we detected using miRNA microarray were suggested to be closely connected with memory function. [score:7]
Hippocampus and blood expression levels of miR-1188a, miR-331 and miR-375 decreased in memory-impaired rats (TLE-MI) compared with control rats (TEL-C). [score:2]
[1 to 20 of 3 sentences]
11
[+] score: 19
In addition, the larger list of mRNA targets of mouse miR-375 is comparable to the human list, in terms of gene. [score:3]
Mir375 is also involved in regulating insulin expression and secretion. [score:3]
Mir375, specifically expressed in islet cells, is believed to play a role in the early stages of islet development, particularly as the embryonic stem cells differentiate into liver and insulin secretory cells [48]. [score:3]
Several, including Mir375, are differentially expressed in T2D patients and rodent mo dels such as the obese diabetic mouse and the GK rat. [score:2]
The only validated mRNA target of rat Mir375 is Pdk1, also validated for the human and mouse microRNA 375. [score:2]
And Mir375 is one of a number of involved in insulin synthesis and secretion (for instance Mir9 and Mir29a/b/c), insulin sensitivity in target tissue (Mir143 and Mir29) or glucose and lipid metabolism (Mir103/107 and Mir122) and thus, having potential roles in diabetes [see for instance, [52], [53]. [score:2]
The promoter region of MIR-375 contains binding sites for ONECUT1, (also known as HNF6) and INSM1 transcription factors, both important for the development of pancreatic islets. [score:2]
The results for the human MIR375 are shown [Fig.  10 and insets]. [score:1]
Interestingly, NEUROD1 and possibly PDX1 may have a role in the transcription of MIR-375—a microRNA associated with pancreatic function [48]. [score:1]
[1 to 20 of 9 sentences]
12
[+] score: 17
We may find some hints as to the mechanism of exocytosis in the lung if we find more targets of miR-375 or any of the components that interact with these targets. [score:5]
The expression of mmu-miR-375 was reported to be limited to the pancreatic β cells, although we also detected it in the rat lung. [score:3]
For example, mmu-miR-375 is a newly identified miRNA expressed highly in the lung. [score:3]
Mtpn was validated as a target gene of mmu-miR-375. [score:3]
Among the 12 miRNAs confirmed by the Northern blots, none has a known function except mmu-miR-375 [28]. [score:1]
We suspect that mmu-miR-375 works in both of these exocytosis processes. [score:1]
Neither the secondary signals nor the actin filament network are affected by mmu-miR-375. [score:1]
[1 to 20 of 7 sentences]
13
[+] score: 17
Using these hepatocyte and non-hepatocyte cell lines and primary tissues, we performed unsupervised clustering analysis by selecting 7 down-regulated miRNAs (miR-17-5p, miR-18a, miR-93, miR-106a, miR-106b, miR-130b and miR-375) and 4 up-regulated miRNAs (miR-21, miR-22, miR-122a and miR-182). [score:7]
Both up-regulated miRNAs (miR-21, miR-22, miR-122a and miR-182) and down-regulated miRNAs (miR-17-5p, miR-18a, miR-93, miR-106a, miR-106b, miR-130b and miR-375) were chosen as a parameter for comparison. [score:7]
2) Some miRNAs, including let-7 family (let-a, -b and -c), miR-16, miR-23b, miR-26, miR-31 and miR-375, were always highly expressed either before or after transdifferentiation (data not shown). [score:3]
[1 to 20 of 3 sentences]
14
[+] score: 16
Expression of miR-375 is often down-regulated in salivary cancer cells [43]. [score:6]
As development proceeds, the observed increases of miR-29c, miR-375, miR-148, and miR-200c may drive the observed decreased expression of Klf4 mRNA. [score:4]
Its target gene, Plag1, is a transcription factor which stimulates proliferation, and the increase of miR-375 may therefore contribute to decreased proliferation during differentiation. [score:3]
The miRNA with the largest expression change, miR-375, increased more than 800-fold. [score:3]
[1 to 20 of 4 sentences]
15
[+] score: 15
The presented data indicate that, among others, the activation takes place due to the opposed expression profile of genes and their regulating microRNAs at the site of inflammation (Figure 6); while the expression of all tested mesenchymal markers (Egr1, Fgf2, Fgf7, Jak2, Notch2, Hif1 α, Zeb2, Mmp9, Lox, and Vim) was significantly induced, microRNAs regulating their expression decreased (miR-192, miR-143, miR-375, miR-30a, miR-107, miR-200b, and miR-125a). [score:9]
Ding et al. earlier demonstrated that miR-375 directly targets the Jak2 oncogene, thereby regulating cancer cell proliferation [21]. [score:5]
In our mo del, the amount of miR-375 was significantly decreased in the inflamed region, while elevated in the TNBS treated uninflamed sections (Figure 3(d)). [score:1]
[1 to 20 of 3 sentences]
16
[+] score: 12
We selected up-regulation of oncogenic miRNAs such as mir-21 as well as down-regulation of the tumor suppressor miRNAs Let-7e, mir-135a, and mir-375 for our analysis. [score:9]
Moreover, the oncogenic miRNA, mir-21 was increased 3.8 fold, whereas the tumor suppressor miRNAs, Let-7e, mir-135a, and mir-375 were decreased by 2.9, 2.7 and 5.9 fold, respectively. [score:3]
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17
[+] score: 9
Both miR-375 and miR-223 play roles in regulating inflammation [52] but exhibited very different, sex-biased expression in the kidney, with miR-375 showing female-biased expression at 15 weeks of age (Table  2) and miR-223 showing male-biased expression at old age (Table  3 and Figure  7). [score:8]
Old age -associated miRNAs showed enrichment in pathways related to endocrine system disorders (miR-129-1, miR-375, miR-223, miR-664, miR-29b, miR-34a), cancer (miR-223, miR-29b, miR-375, miR-96), and cellular movement/invasion of cells (miR-29b, miR-29c, miR-7a, miR-96, miR-34a, miR-375). [score:1]
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18
[+] score: 8
Among them, miR-375 that is abundantly expressed in pancreatic and beta cells, negatively regulates glucose-stimulated insulin secretion via myotrophin (Mtpn) inhibition [31], [32]. [score:6]
The authors investigated the expression of seven diabetes-related miRNAs (miR-9, miR-29a, miR-30d, miR-34a, miR-124a, miR-146a and miR-375), four (miR-29a, miR-30d, miR-175 and miR-146a) of which were also found to be dysregulated in our study. [score:2]
[1 to 20 of 2 sentences]
19
[+] score: 7
Other miRNAs from this paper: mmu-mir-1a-1, mmu-mir-127, mmu-mir-134, mmu-mir-136, mmu-mir-154, mmu-mir-181a-2, mmu-mir-143, mmu-mir-196a-1, mmu-mir-196a-2, mmu-mir-21a, rno-mir-329, mmu-mir-329, mmu-mir-1a-2, mmu-mir-181a-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-375, mmu-mir-379, mmu-mir-181b-2, rno-mir-21, rno-mir-127, rno-mir-134, rno-mir-136, rno-mir-143, rno-mir-154, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-196a, rno-mir-181a-1, mmu-mir-196b, rno-mir-196b-1, mmu-mir-412, mmu-mir-370, oar-mir-431, oar-mir-127, oar-mir-432, oar-mir-136, mmu-mir-431, mmu-mir-433, rno-mir-431, rno-mir-433, ssc-mir-181b-2, ssc-mir-181c, ssc-mir-136, ssc-mir-196a-2, ssc-mir-21, rno-mir-370, rno-mir-412, rno-mir-1, mmu-mir-485, mmu-mir-541, rno-mir-541, rno-mir-493, rno-mir-379, rno-mir-485, mmu-mir-668, bta-mir-21, bta-mir-181a-2, bta-mir-127, bta-mir-181b-2, bta-mir-181c, mmu-mir-181d, mmu-mir-493, rno-mir-181d, rno-mir-196c, mmu-mir-1b, bta-mir-1-2, bta-mir-1-1, bta-mir-134, bta-mir-136, bta-mir-143, bta-mir-154a, bta-mir-181d, bta-mir-196a-2, bta-mir-196a-1, bta-mir-196b, bta-mir-329a, bta-mir-329b, bta-mir-370, bta-mir-375, bta-mir-379, bta-mir-412, bta-mir-431, bta-mir-432, bta-mir-433, bta-mir-485, bta-mir-493, bta-mir-541, bta-mir-181a-1, bta-mir-181b-1, ssc-mir-1, ssc-mir-181a-1, mmu-mir-432, rno-mir-668, ssc-mir-143, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-196b-1, ssc-mir-127, ssc-mir-432, oar-mir-21, oar-mir-181a-1, oar-mir-493, oar-mir-433, oar-mir-370, oar-mir-379, oar-mir-329b, oar-mir-329a, oar-mir-134, oar-mir-668, oar-mir-485, oar-mir-154a, oar-mir-154b, oar-mir-541, oar-mir-412, mmu-mir-21b, mmu-mir-21c, ssc-mir-196a-1, ssc-mir-196b-2, ssc-mir-370, ssc-mir-493, bta-mir-154c, bta-mir-154b, oar-mir-143, oar-mir-181a-2, chi-mir-1, chi-mir-127, chi-mir-134, chi-mir-136, chi-mir-143, chi-mir-154a, chi-mir-154b, chi-mir-181b, chi-mir-181c, chi-mir-181d, chi-mir-196a, chi-mir-196b, chi-mir-21, chi-mir-329a, chi-mir-329b, chi-mir-379, chi-mir-412, chi-mir-432, chi-mir-433, chi-mir-485, chi-mir-493, rno-mir-196b-2, bta-mir-668, ssc-mir-375
For example, miR-273 and the lys-6 miRNA have been shown to be involved in the development of the nervous system in nematode worm [3]; miR-430 was reported to regulate the brain development of zebrafish [4]; miR-181 controlled the differentiation of mammalian blood cell to B cells [5]; miR-375 regulated mammalian islet cell growth and insulin secretion [6]; miR-143 played a role in adipocyte differentiation [7]; miR-196 was found to be involved in the formation of mammalian limbs [8]; and miR-1 was implicated in cardiac development [9]. [score:6]
Most of the miRNAs were sequenced only a few times, whereas miR-127, miR-154 and miR-375 were sequenced thousands of times. [score:1]
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20
[+] score: 7
Interestingly expression of miR-571 was not detected in mouse islets as compared to the highly expressed miR375 (data not shown). [score:4]
Data are presented respect to miR375 expression levels. [score:3]
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21
[+] score: 5
Amylase and lipase increases were noted from 1–8 h in rats in both 15 and 50 μg/kg dose groups while pancreatic necrosis was noted at 8, 24 and 48 h. MiR-375-3p has been reported to be enriched in islets and the miRNA with the highest intra-islet expression [38] and in our study was increased from 4–24 h in the 15 and 50 μg/kg groups, returning to approximately vehicle level by 48 h. MiR-216a-5p and miR-217-5p remained elevated in the serum of rats longer than amylase or lipase and had a much greater dynamic range which could be advantageous if detection of pancreatic injury is not able to be examined at earlier time points. [score:3]
The tissue specificity/enrichment of many other tissue enriched miRNAs including muscle and heart enriched miRs-133a-3p, 499-5p, miR-1a-3p as well as pancreas enriched miRs-216a-5p, 217-5p and miR-375-3p were confirmed [38– 40] (Fig.   4). [score:1]
MiR-375-3p was increased from 4–24 h in the 15 and 50 μg/kg groups and returned to approximately vehicle level by 48 h. The pancreas enriched miRNAs conserved between rat and dog (miR-101c, 141-3p, 148a-3p, 193b-3p, 200c-3p,) that were tested displayed increases in the serum similar to amylase (data not shown), whereas miRs 320-3p, 4286 and 5100 were not increased (Fig.   7 and statistical analysis Additional file 15: Table S7). [score:1]
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22
[+] score: 4
In addition, compared to F0-N rats, stress in F0-S dams induced one miRNA (rno-miR-466b-1-3p) and suppressed the expression of three miRNAs (rno-miR-145-3p, rno-miR-24-1-5p and rno-miR-375) (all Ps <0.10). [score:4]
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23
[+] score: 4
MiR-375 is one of few miRNAs (along with miR-7) expressed mainly in adult islets and only marginally elsewhere [10]– [13], and controls a cluster of genes regulating cellular growth and proliferation, evident from studies of miR-375 [(−/−)] mice, which are hyperglycemic and have decreased beta-cell mass [11]. [score:4]
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24
[+] score: 4
Regarding β cell reprogramming, co-transfection of miR-302 and PNM have been shown to induce the reprogramming of human hepatocytes into pancreatic progenitor cells [22], and lentiviral -mediated expression of miR-375 in iPSCs promoted the differentiation of these cells into insulin-producing islet-like clusters [23]. [score:3]
Regarding β cell reprogramming, performing a co-transfection of miRNA-302 and PNM has been recently reported to improve the reprogramming efficiency of cells from a human hepatocyte cell line into pancreatic progenitor cells [22], and miRNA-375 was reported to promote β pancreatic differentiation in human induced pluripotent stem (hiPS) cells [23]. [score:1]
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25
[+] score: 4
Two of the other miRNAs, miR-375 and miR-494, also showed the same pattern of up-regulation in LII without reaching statistical significance in the layered samples. [score:4]
[1 to 20 of 1 sentences]
26
[+] score: 3
In particular, using murine mo dels, miR-9 and miR-375 are reported to be involved in regulation of insulin secretion [16, 17], while miR-124a2 has recently been implicated in pancreatic beta-cell development and function [18]. [score:3]
[1 to 20 of 1 sentences]
27
[+] score: 3
Blocking miR-375 expression increases PDK1 protein level and glucose-stimulatory action on insulin mRNA and DNA synthesis [8, 9]. [score:3]
[1 to 20 of 1 sentences]
28
[+] score: 3
In hippocampus, a total of 475 targets of rno-miR-101b-3p, rno-miR-217-5p, rno-miR-375-3p, rno-miR-20a-5p, rno-miR-19b-3p, and rno-miR-182 were predicted. [score:3]
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29
[+] score: 3
The expression of six (miR-29a, miR-29b, miR-29c, miR-34a, miR-375, and miR-466b-2*) was altered in both males and females (Table  1). [score:3]
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[+] score: 3
For example, miR-325-3p is associated with the immobilization -induced suppression of LH secretion [11], and miR-375 is involved in ATCH secretion [27]. [score:3]
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Mice lacking microRNA-375 (375 KO) share some characteristics with our DEX rats (e. g., hyperglycemia, fast and fed hyperglucagonemia, glucose intolerance and reduced effect of glucose to inhibit glucagon secretion) [33]. [score:1]
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Other miRNAs from this paper: hsa-mir-375
Biochanin A promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in breast cancer cells. [score:1]
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These included miR-20a, miR-18b, miR-375, and miR-215 [34]. [score:1]
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Moreover, we confirmed the absence of changes in miRNAs affected by maternal (mir375) [37] or paternal stress (mir30a and mir204) [38]. [score:1]
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[8] These miRNAs include miR-26a, miR-203, miR-22, miR-375, and other. [score:1]
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5 mmu-miR-214 -1.7 -6.1 -10.9 mmu-miR-137 -31.7 -6.8 -144.8 mmu-miR-29c -1.8 -10.5 -10.7 rno-miR-532–5p -2.0 -59.1 -126.9 mmu-miR-466d-3p -2.7 -4.2 -9.9 mmu-miR-466d-5p -23.2 -64.7 -105.7 mmu-miR-22 -1.6 -4.6 -9.9 mmu-miR-582–5p -21.3 -59.4 -97.1 mmu-miR-690 -1.9 -2.1 -9.7 rno-miR-421 -21.3 -59.3 -97.0 mmu-miR-193 -4.9 -3. 5 -8.1 mmu-miR-369–5p -20.9 -58.3 -95.3 mmu-miR-27b* -2.1 -2.9 -8.0 mmu-miR-684 -20.8 -58.1 -94.9 mmu-miR-378 -1.6 -4.6 -7.7 mmu-miR-375 -20.6 -57.6 -94.2 mmu-miR-9* -1.9 -18.4 -7.7 mmu-miR-337–5p -20.5 -57.4 -93.8 mmu-miR-204 -2.5 -5.3 -7.5 mmu-miR-15a* -20.3 -56.8 -92.8 mmu-miR-28* -1.9 -3.2 -6.5 mmu-miR-532–5p -19. [score:1]
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On the other hand, other miRNAs such as, let-7i, miR-143, miR-148b-3p, miR-15b, miR-17-5p, miR-24, miR-27b, miR-92a, miR-106b, miR-125b-5p, miR-181a, miR-181c, miR-181d, miR-200c, miR-375, miR-107, miR-141, and miR-370, were present at higher levels in colostrum whey than in mature milk whey (Fig. 6). [score:1]
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