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Page 2 of 7 Qu et al. Neuroimmunol Neuroinflammation 2018;5:10 I http://dx.doi.org/10.20517/2347-8659.2018.01

EGFL7
RAN polymerase II

Pri-mir-126 Pre-mir-126 Pre-mir-126
Drosha

mir-126

RISC
Cytoplasm mRNA

Figure 1. MiR-126 is located in the 7th intron of EGFL7. RNA polymerase II binded with EGFL7, resulting in the pri-miR-126 formation.
Pri-miRNA-126 targeted to Drosha for cleavage, giving birth to pre-miR-126. Pre-miR-126 was transferred from nucleus to cytoplasm
by exporting 5, in which it matured into miR-126. The Dicer cleaved miR-126 into single-strand and either strand of the duplex may
potentially act as a functional miRNA, integrating into RISC. The RISC with a microRNA recognized complementary mRNA molecules and
degraded or silenced them, resulting in substantially decreased levels of protein translation and effectively inhibiting the gene. EGFL7:
epidermal growth factor-like-domain 7 gene; RISC: RNA-induced silencing complex

enzyme Drosha, the pri-miR-126 generates shorter stem-loop precursors (pre-miRNA). Pre-miR-126 is
[3]
exported to the cytoplasm by exportin-5 . In the cytoplasm, RNase III enzyme Dicer processes pre-
miR-126 into mature 20-24 nucleotides miRNAs, which then incorporates to the RNA-induced silencing
complex (RISC, Figure 1).

MiR-126 is specifically and highly expressed in the endothelial cells (ECs), which regulates ECs migration,
[4]
cytoskeleton reorganization, capillary network stability, cell survival and apoptosis . And microRNA-126
regulates cell survival or apoptosis, depending on different cell types. Furthermore, miR-126 is necessary
[5]
for the maintenance of vascular structure in vivo .

MIR-126 PROMOTES ANGIOGENESIS AFTER ISCHEMIC STROKE
[6]
Ischemic stroke was one of the major causes of death and disability in the worldwide . It was classified into
large-artery, cardioembolic, and small-vessel (lacunar stroke) ischemic stroke . Currently, angiogenesis
[7]
was regarded as a promising therapy for the repairing and remodeling after ischemic stroke. Angiogenesis
is the growth and remodeling process of the primitive vascular network. Angiogenesis is involved in
[8]
enlargement of pre-existing vessels or formation of capillaries through trans-endothelial cell bridges .
Angiogenesis attenuated functional deficits and promoted behavioral recovery may through restoring the
blood flow in the ischemic area. In recent years, studies demonstrated that deletion of miR-126 in mice
embryo and zebra fish embryo reduced the integrity of vessels and decreased postnatal angiogenesis .
[5,9]

MiR-126 regulated the response of ECs to vascular endothelial growth factor (VEGF), which was via
directly repressing negative regulators of VEGF pathway. The negative regulators were the Sprout-related
[5]
EVH1 domain-containing protein 1 (SPRED1) and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) .
MiR-126 was an important factor, which could maintain the vascular integrity. Antago-miR-126 decreases
ischemia-induced angiogenesis in hind-limb ischemia by increasing SPRED1 and PIK3R2 [Figure 2] .
[10]