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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

miR-107 enhances tubular formation and migration of RBMECs and HUVECs in vitro.(A) Top: Representative photomicrographs of tube formation of HUVECs transfected with miR-107 or scr-miR and un-transfected HUVECs (control). Tube formation was measured after 12 hours under normoxia. Bottom: Tube formation capacity of HUVECs transfected with anti-miR-107 or scr-miR and un-transfected HUVECs (sham). The anti-miR-107 effect was investigated under OGD for 12 h. Total magnification, ×100 (B) the number of tubule branches per field. (C) The cumulative sprout length per field. (D–F) RBMECs (G) Top: RBMECs transfected with miR-107 or scr-miR and un-transfected RBMECs (control) were incubated on a Transwell system under normoxia. Bottom: RBMECs transfected with anti-miR-107 or scr-miR and un-transfected RBMECs (sham) were incubated on a Transwell system under OGD. The number of migrating cells was determined after 12 hours. (H) Quantification of the migration is expressed as the number of migrating cells per high-power field. (I,J) HUVECs. (K) The effect of miR-107 overexpression under normoxia on HUVECs migration was determined by scratch wound assay. Wound closure was determined after 12 hours. White lines indicate edges of scratch wounds. Representative photomicrographs showed migration. (L) Quantization of HUVECs migration. Data are presented as mean ± SD. *P < 0.05, vs. control group under normoxia, #P < 0.05, vs. sham group subjected to OGD.
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f2: miR-107 enhances tubular formation and migration of RBMECs and HUVECs in vitro.(A) Top: Representative photomicrographs of tube formation of HUVECs transfected with miR-107 or scr-miR and un-transfected HUVECs (control). Tube formation was measured after 12 hours under normoxia. Bottom: Tube formation capacity of HUVECs transfected with anti-miR-107 or scr-miR and un-transfected HUVECs (sham). The anti-miR-107 effect was investigated under OGD for 12 h. Total magnification, ×100 (B) the number of tubule branches per field. (C) The cumulative sprout length per field. (D–F) RBMECs (G) Top: RBMECs transfected with miR-107 or scr-miR and un-transfected RBMECs (control) were incubated on a Transwell system under normoxia. Bottom: RBMECs transfected with anti-miR-107 or scr-miR and un-transfected RBMECs (sham) were incubated on a Transwell system under OGD. The number of migrating cells was determined after 12 hours. (H) Quantification of the migration is expressed as the number of migrating cells per high-power field. (I,J) HUVECs. (K) The effect of miR-107 overexpression under normoxia on HUVECs migration was determined by scratch wound assay. Wound closure was determined after 12 hours. White lines indicate edges of scratch wounds. Representative photomicrographs showed migration. (L) Quantization of HUVECs migration. Data are presented as mean ± SD. *P < 0.05, vs. control group under normoxia, #P < 0.05, vs. sham group subjected to OGD.

Mentions: The Matrigel assay demonstrated that HUVECs and RBMECs transfected with miR-107-overexpressing lentiviral vector (miR-107 group) were found to have enhanced tubular formation, as indicated by increased number of branch points, and most prominently, by increased tubular length (by 7.98 fold and 4.39 fold, P < 0.05), as compared with negative-control scramble lentivirus transfected cells (scr-miR group; negative control group) and un-transfected cells (control group) under normoxia (Fig. 2A–F, P < 0.05). On the other hand, the miR-107-downregulating lentiviral vector (anti-miR-107) transfected HUVECs and RBMECs expressed lower levels of miR-107 resulting in reduction of tubular length by 14.67 fold and 10.11 fold under OGD (Fig. 2A–F, P < 0.05). No significant effect on cell migration capacity was detected after transfection with negative-control scramble lentivirus or in un-transfected cells (Fig. 2A–F, P < 0.05).


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)

miR-107 enhances tubular formation and migration of RBMECs and HUVECs in vitro.(A) Top: Representative photomicrographs of tube formation of HUVECs transfected with miR-107 or scr-miR and un-transfected HUVECs (control). Tube formation was measured after 12 hours under normoxia. Bottom: Tube formation capacity of HUVECs transfected with anti-miR-107 or scr-miR and un-transfected HUVECs (sham). The anti-miR-107 effect was investigated under OGD for 12 h. Total magnification, ×100 (B) the number of tubule branches per field. (C) The cumulative sprout length per field. (D–F) RBMECs (G) Top: RBMECs transfected with miR-107 or scr-miR and un-transfected RBMECs (control) were incubated on a Transwell system under normoxia. Bottom: RBMECs transfected with anti-miR-107 or scr-miR and un-transfected RBMECs (sham) were incubated on a Transwell system under OGD. The number of migrating cells was determined after 12 hours. (H) Quantification of the migration is expressed as the number of migrating cells per high-power field. (I,J) HUVECs. (K) The effect of miR-107 overexpression under normoxia on HUVECs migration was determined by scratch wound assay. Wound closure was determined after 12 hours. White lines indicate edges of scratch wounds. Representative photomicrographs showed migration. (L) Quantization of HUVECs migration. Data are presented as mean ± SD. *P < 0.05, vs. control group under normoxia, #P < 0.05, vs. sham group subjected to OGD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4543985&req=5

f2: miR-107 enhances tubular formation and migration of RBMECs and HUVECs in vitro.(A) Top: Representative photomicrographs of tube formation of HUVECs transfected with miR-107 or scr-miR and un-transfected HUVECs (control). Tube formation was measured after 12 hours under normoxia. Bottom: Tube formation capacity of HUVECs transfected with anti-miR-107 or scr-miR and un-transfected HUVECs (sham). The anti-miR-107 effect was investigated under OGD for 12 h. Total magnification, ×100 (B) the number of tubule branches per field. (C) The cumulative sprout length per field. (D–F) RBMECs (G) Top: RBMECs transfected with miR-107 or scr-miR and un-transfected RBMECs (control) were incubated on a Transwell system under normoxia. Bottom: RBMECs transfected with anti-miR-107 or scr-miR and un-transfected RBMECs (sham) were incubated on a Transwell system under OGD. The number of migrating cells was determined after 12 hours. (H) Quantification of the migration is expressed as the number of migrating cells per high-power field. (I,J) HUVECs. (K) The effect of miR-107 overexpression under normoxia on HUVECs migration was determined by scratch wound assay. Wound closure was determined after 12 hours. White lines indicate edges of scratch wounds. Representative photomicrographs showed migration. (L) Quantization of HUVECs migration. Data are presented as mean ± SD. *P < 0.05, vs. control group under normoxia, #P < 0.05, vs. sham group subjected to OGD.
Mentions: The Matrigel assay demonstrated that HUVECs and RBMECs transfected with miR-107-overexpressing lentiviral vector (miR-107 group) were found to have enhanced tubular formation, as indicated by increased number of branch points, and most prominently, by increased tubular length (by 7.98 fold and 4.39 fold, P < 0.05), as compared with negative-control scramble lentivirus transfected cells (scr-miR group; negative control group) and un-transfected cells (control group) under normoxia (Fig. 2A–F, P < 0.05). On the other hand, the miR-107-downregulating lentiviral vector (anti-miR-107) transfected HUVECs and RBMECs expressed lower levels of miR-107 resulting in reduction of tubular length by 14.67 fold and 10.11 fold under OGD (Fig. 2A–F, P < 0.05). No significant effect on cell migration capacity was detected after transfection with negative-control scramble lentivirus or in un-transfected cells (Fig. 2A–F, P < 0.05).

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