Background:
Diabetic retinopathy (DR) is currently the leading cause of
blindness and visual disability in adults with
diabetes mellitus (DM). Neovascularization has been identified as an important clinical property in DR, however, the exact mechanisms in DR neovascularization are still unclear and need further elucidation.Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of
long non-coding RNA (
lncRNA)-
metastasis associated
lung adenocarcinoma transcript 1 (MALAT1), miR-125b and
vascular endothelial-cadherin (
VE-cadherin) in human retina microvascular endothelial cells (hRMECs) treated with high
glucose (HG).
Luciferase assay was used to detect interaction of MALAT1 with miR-125b and miR-125b with
VE-cadherin. MTT assay, transwell assay, tube formation assay and vascular permeability assay were conducted to detect the cell viability, migration tube formation ability and permeability of hRMECs, respectively. ELISA was used to examine the release of
VE-cadherin and
vascular endothelial growth factor (
VEGF). Western blotting was used to access the
protein expression of
VE-cadherin,
VEGF, β-
catenin,
matrix metalloproteinase (
MMP) 2 (MMP2) and MMP9.Results: MALAT1 and
VE-cadherin were up-regulated while miR-125b was down-regulated in hRMECs treated with HG. MALAT1 could competitively bind to miR-125b against
VE-cadherin at the site of 3'-untranslated region (3'-UTR), leading to the up-regulation of
VE-cadherin. Knockdown of MALAT1 inhibited the proliferation, migration, tube formation and vascular permeability of hRMECs induced by HG through up-regulating miR-125b. Furthermore, we found the deletion of MALAT1 suppressed the
VE-cadherin/β-
catenin complex and neovascularization related
proteins expression, which was up-regulated by HG.Conclusion: Knockdown of MALAT1 inhibited cell proliferation, migration and angiogenesis of hRMECs via suppressing the
VE-cadherin/β-
catenin complex through targeting miR-125b. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic
therapy for DR.