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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 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.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.
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Related In: Results  -  Collection

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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).

Bottom Line: 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.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