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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 regulates the expression of endogenous VEGF165 or VEGF164 via Dicer-1 by miR-107.(A) Representative picture and analysis diagram show the protein levels of VEGF165 or Dicer-1 in HUVECs as determined by Western blotting. (B) The expression of Dicer-1 was decrease in the miR-107-transfected HUVECs. Under hypoxia, down-regulation of Dicer-1 could strongly induce mRNA expression of VEGF165 in anti-miR-107-transfected HUVECs. (C,D) RBMECs. (E) Schematic illustration of target supression by miR-107 (left), target desupression by anti-miR-107 treatment (center), and inhibition of the latter by lentivirus-mediated RNA interference with Dicer-1 (right). Data are presented as mean ± SD. *P < 0.05, vs. control group, #P < 0.05, vs. anti-miR-107 group.
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f5: miR-107 regulates the expression of endogenous VEGF165 or VEGF164 via Dicer-1 by miR-107.(A) Representative picture and analysis diagram show the protein levels of VEGF165 or Dicer-1 in HUVECs as determined by Western blotting. (B) The expression of Dicer-1 was decrease in the miR-107-transfected HUVECs. Under hypoxia, down-regulation of Dicer-1 could strongly induce mRNA expression of VEGF165 in anti-miR-107-transfected HUVECs. (C,D) RBMECs. (E) Schematic illustration of target supression by miR-107 (left), target desupression by anti-miR-107 treatment (center), and inhibition of the latter by lentivirus-mediated RNA interference with Dicer-1 (right). Data are presented as mean ± SD. *P < 0.05, vs. control group, #P < 0.05, vs. anti-miR-107 group.

Mentions: To confirm that miR-107 exerts its effect on angiogenesis through down-regulation of Dicer-1, we designed a strategy (Fig. 5E) to validate the functional relevance of those downstream target genes. If Dicer-1 was responsible for the effect of miR-107 on VEGF165, RNA interference with Dicer-1 expression (by lentivirus transfection) should specifically counteract the effect of anti-miR-107 in the expression of Dicer and VEGF165. This concept was tested by transfecting HUVECs in vitro with miR-107-downregulating lentivirus (anti-miR-107) and Dicer-1-downregulating lentivirus (anti-Dicer-1) to reduce the expression of miR-107 and Dicer-1 (Fig. 5C, P < 0.05). We found that suppressed Dicer-1 expression (Fig. 5A–D, P < 0.05) in anti-miR-107 transfected HUVECs under OGD resulted in strong induction of VEGF165 expression (Fig. 5A–D, P < 0.05), confirming that, under hypoxia, miR-107 induced VEGF165 expression by suppressing Dicer-1.


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 regulates the expression of endogenous VEGF165 or VEGF164 via Dicer-1 by miR-107.(A) Representative picture and analysis diagram show the protein levels of VEGF165 or Dicer-1 in HUVECs as determined by Western blotting. (B) The expression of Dicer-1 was decrease in the miR-107-transfected HUVECs. Under hypoxia, down-regulation of Dicer-1 could strongly induce mRNA expression of VEGF165 in anti-miR-107-transfected HUVECs. (C,D) RBMECs. (E) Schematic illustration of target supression by miR-107 (left), target desupression by anti-miR-107 treatment (center), and inhibition of the latter by lentivirus-mediated RNA interference with Dicer-1 (right). Data are presented as mean ± SD. *P < 0.05, vs. control group, #P < 0.05, vs. anti-miR-107 group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: miR-107 regulates the expression of endogenous VEGF165 or VEGF164 via Dicer-1 by miR-107.(A) Representative picture and analysis diagram show the protein levels of VEGF165 or Dicer-1 in HUVECs as determined by Western blotting. (B) The expression of Dicer-1 was decrease in the miR-107-transfected HUVECs. Under hypoxia, down-regulation of Dicer-1 could strongly induce mRNA expression of VEGF165 in anti-miR-107-transfected HUVECs. (C,D) RBMECs. (E) Schematic illustration of target supression by miR-107 (left), target desupression by anti-miR-107 treatment (center), and inhibition of the latter by lentivirus-mediated RNA interference with Dicer-1 (right). Data are presented as mean ± SD. *P < 0.05, vs. control group, #P < 0.05, vs. anti-miR-107 group.
Mentions: To confirm that miR-107 exerts its effect on angiogenesis through down-regulation of Dicer-1, we designed a strategy (Fig. 5E) to validate the functional relevance of those downstream target genes. If Dicer-1 was responsible for the effect of miR-107 on VEGF165, RNA interference with Dicer-1 expression (by lentivirus transfection) should specifically counteract the effect of anti-miR-107 in the expression of Dicer and VEGF165. This concept was tested by transfecting HUVECs in vitro with miR-107-downregulating lentivirus (anti-miR-107) and Dicer-1-downregulating lentivirus (anti-Dicer-1) to reduce the expression of miR-107 and Dicer-1 (Fig. 5C, P < 0.05). We found that suppressed Dicer-1 expression (Fig. 5A–D, P < 0.05) in anti-miR-107 transfected HUVECs under OGD resulted in strong induction of VEGF165 expression (Fig. 5A–D, P < 0.05), confirming that, under hypoxia, miR-107 induced VEGF165 expression by suppressing Dicer-1.

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