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MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B - Sci Rep (2015)

Bottom Line: We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats.This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke.This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

ABSTRACT
Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

No MeSH data available.


Related in: MedlinePlus

Regulation of the expression of endogenous VEGF165 or VEGF164 by miR-107.(A,B) qRT-PCR showed the mRNA levels of VEGF164 and VEGF120 in rats IBZ on 3rd and 7th days after pMCAO compared with sham-operated group (control). Data are presented as mean ± SD. *P < 0.05, vs. control group. (C) Rats after pMCAO were injected with agomir (agomir-107) or negative control (scr-miR). qRT-PCR results showed that agomir-107 increased VEGF164 and VEGF120 expression in IBZ on day 3 and day 7 , compared with negative control (scr-miR) and control group. Data are presented as mean ± SD. *P < 0.05, vs. control group (D) qRT-PCR data of VEGF165 in HUVECs from over-expression of miR-107 under normoxia and down-regulation of miR-107 under OGD for 12 h (E) qRT-PCR data of VEGF164 in RBMECs (F) qRT-PCR data of VEGF164 in astrocytes. (G) Representative pictures and analysis diagram showing the protein levels of VEGF165 in HUVECs as determined by Western blotting. Data are presented as mean ± SD. *P < 0.05, vs. control group, ΔP < 0.05, vs. sham group subjected to OGD.
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f3: Regulation of the expression of endogenous VEGF165 or VEGF164 by miR-107.(A,B) qRT-PCR showed the mRNA levels of VEGF164 and VEGF120 in rats IBZ on 3rd and 7th days after pMCAO compared with sham-operated group (control). Data are presented as mean ± SD. *P < 0.05, vs. control group. (C) Rats after pMCAO were injected with agomir (agomir-107) or negative control (scr-miR). qRT-PCR results showed that agomir-107 increased VEGF164 and VEGF120 expression in IBZ on day 3 and day 7 , compared with negative control (scr-miR) and control group. Data are presented as mean ± SD. *P < 0.05, vs. control group (D) qRT-PCR data of VEGF165 in HUVECs from over-expression of miR-107 under normoxia and down-regulation of miR-107 under OGD for 12 h (E) qRT-PCR data of VEGF164 in RBMECs (F) qRT-PCR data of VEGF164 in astrocytes. (G) Representative pictures and analysis diagram showing the protein levels of VEGF165 in HUVECs as determined by Western blotting. Data are presented as mean ± SD. *P < 0.05, vs. control group, ΔP < 0.05, vs. sham group subjected to OGD.

Mentions: The mRNA expression level of VEGF164 was increased in IBZ on day 3 and day 7 after pMCAO in rats, presenting the same trend as that with miR-107 (Fig. 3A,B, P < 0.05). Further qRT-PCR detection showed that up-regulation of miR-107 level by lateral ventricular injection of agomir-107, a synthetic double stranded miR-107 mimics, in pMCAO rats increased the level of VEGF164 as compared with agomir control (agomir-ctl) group on day 3 and day 7 in IBZ (Fig. 3C, P < 0.05). Figure 3D,E showed that miR-107 up-regulation in HUVECs and RBMECs also raised the levels of endogenous VEGF165 or VEGF164 as compared with scr-miR. Likewise, down-regulation of miR-107 by transfection with anti-miR-107 decreased the expression of endogenous VEGF165 or VEGF164 in HUVECs and RBMECs (Fig. 3D,E, P < 0.05). However, miR-107 had little effect on astrocytes in terms of VEGF164 secretion as compared with scr-miR (Fig. 3F, P > 0.05). Similarly, we detected the protein expression level of VEGF165 in HUVECs. Compared with the control group and negative control group (scr-miR), the relative expression of VEGF165 (in the western blot assay) was increased in the miR-107 group and decreased in the anti-miR-107 group (Fig. 3G).


MicroRNA-107 contributes to post-stroke angiogenesis by targeting Dicer-1.

Li Y, Mao L, Gao Y, Baral S, Zhou Y, Hu B - Sci Rep (2015)

Regulation of the expression of endogenous VEGF165 or VEGF164 by miR-107.(A,B) qRT-PCR showed the mRNA levels of VEGF164 and VEGF120 in rats IBZ on 3rd and 7th days after pMCAO compared with sham-operated group (control). Data are presented as mean ± SD. *P < 0.05, vs. control group. (C) Rats after pMCAO were injected with agomir (agomir-107) or negative control (scr-miR). qRT-PCR results showed that agomir-107 increased VEGF164 and VEGF120 expression in IBZ on day 3 and day 7 , compared with negative control (scr-miR) and control group. Data are presented as mean ± SD. *P < 0.05, vs. control group (D) qRT-PCR data of VEGF165 in HUVECs from over-expression of miR-107 under normoxia and down-regulation of miR-107 under OGD for 12 h (E) qRT-PCR data of VEGF164 in RBMECs (F) qRT-PCR data of VEGF164 in astrocytes. (G) Representative pictures and analysis diagram showing the protein levels of VEGF165 in HUVECs as determined by Western blotting. Data are presented as mean ± SD. *P < 0.05, vs. control group, ΔP < 0.05, vs. sham group subjected to OGD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4543985&req=5

f3: Regulation of the expression of endogenous VEGF165 or VEGF164 by miR-107.(A,B) qRT-PCR showed the mRNA levels of VEGF164 and VEGF120 in rats IBZ on 3rd and 7th days after pMCAO compared with sham-operated group (control). Data are presented as mean ± SD. *P < 0.05, vs. control group. (C) Rats after pMCAO were injected with agomir (agomir-107) or negative control (scr-miR). qRT-PCR results showed that agomir-107 increased VEGF164 and VEGF120 expression in IBZ on day 3 and day 7 , compared with negative control (scr-miR) and control group. Data are presented as mean ± SD. *P < 0.05, vs. control group (D) qRT-PCR data of VEGF165 in HUVECs from over-expression of miR-107 under normoxia and down-regulation of miR-107 under OGD for 12 h (E) qRT-PCR data of VEGF164 in RBMECs (F) qRT-PCR data of VEGF164 in astrocytes. (G) Representative pictures and analysis diagram showing the protein levels of VEGF165 in HUVECs as determined by Western blotting. Data are presented as mean ± SD. *P < 0.05, vs. control group, ΔP < 0.05, vs. sham group subjected to OGD.
Mentions: The mRNA expression level of VEGF164 was increased in IBZ on day 3 and day 7 after pMCAO in rats, presenting the same trend as that with miR-107 (Fig. 3A,B, P < 0.05). Further qRT-PCR detection showed that up-regulation of miR-107 level by lateral ventricular injection of agomir-107, a synthetic double stranded miR-107 mimics, in pMCAO rats increased the level of VEGF164 as compared with agomir control (agomir-ctl) group on day 3 and day 7 in IBZ (Fig. 3C, P < 0.05). Figure 3D,E showed that miR-107 up-regulation in HUVECs and RBMECs also raised the levels of endogenous VEGF165 or VEGF164 as compared with scr-miR. Likewise, down-regulation of miR-107 by transfection with anti-miR-107 decreased the expression of endogenous VEGF165 or VEGF164 in HUVECs and RBMECs (Fig. 3D,E, P < 0.05). However, miR-107 had little effect on astrocytes in terms of VEGF164 secretion as compared with scr-miR (Fig. 3F, P > 0.05). Similarly, we detected the protein expression level of VEGF165 in HUVECs. Compared with the control group and negative control group (scr-miR), the relative expression of VEGF165 (in the western blot assay) was increased in the miR-107 group and decreased in the anti-miR-107 group (Fig. 3G).

Bottom Line: We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats.This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke.This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

ABSTRACT
Previous studies have suggested that microRNA-107 (miR-107) regulates cell migration in tumor and promotes Hypoxia Inducible Factor 1α (HIF1α) regulated angiogenesis under hypoxia. We found that miR-107 was strongly expressed in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) in rats and inhibition of miR-107 could reduce capillary density in the IBZ after stroke. Such finding led us to hypothesize that miR-107 might regulate post-stroke angiogenesis and therefore serve as a therapeutic target. We also found that antagomir-107, a synthetic miR-107 inhibitor, decreased the number of capillaries in IBZ and increased overall infarct volume after pMCAO in rats. We demonstrated that miR-107 could directly down-regulate Dicer-1, a gene that encodes an enzyme essential for processing microRNA (miRNA) precursors. This resulted in translational desupression of VEGF (vascular endothelial growth factor) mRNA, thereby increasing expression of endothelial cell-derived VEGF (VEGF165/VEGF164), leading to angiogenesis after stroke. This process might be a protective mechanism for ischemia-induced cerebral injury and miR-107 might be used as a novel tool in stroke treatment.

No MeSH data available.


Related in: MedlinePlus