Curcumin inhibits angiogenesis by up-regulation of microRNA-1275 and microRNA-1246: a promising therapy for treatment of corneal neovascularization.
OBJECTIVE
Curcumin (capable of inhibiting angiogenic growth of human umbilical vein endothelial cells [HUVECs]), can be employed in vitro as a model of pathogenesis of corneal neovascularization (CRNV). The aim of this study was to explore regulatory mechanisms of microRNA (miR) levels after curcumin treatment.


METHODS
Expression profiles of miRs in curcumin-treated HUVECs were investigated by miR microassay. Specific mimics and inhibitors of miR-1275 or miR-1246 were transfected into HUVECs. Then, their target genes, vascular endothelial growth factor B (VEGFB) and nuclear transcription factor kappa B acting protein (NKAP) were detected by quantitative real-time PCR, Western blotting assay or immunofluorescence assay. Cell proliferation and cell cycle parameters were measured with the help of CCK-8 assay and flow cytometry.


RESULTS
MiR-1275 and miR-1246 expression levels were up-regulated by curcumin. Administration of the specific mimics and inhibitors of the two miRs led to significant changes in expression of VEGFB and NKAP as well as the indicators related to angiogenesis. Anti-angiogenic effect of curcumin depended on expression patterns of the two miRs in that inhibition of either miR interfered with the effect of curcumin. Furthermore, overexpression of NKAP interrupted effects of curcumin on the cells.


CONCLUSIONS
Collectively, our findings demonstrate that curcumin inhibited HUVEC proliferation by up-regulation of miR-1275 and miR-1246.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yanhui
Y
Bai
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Weiqun
W
Wang
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Guangli
G
Sun
Department of Ophthalmology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430312, China.
Mingchang
M
Zhang
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. dongjingmin505@163.com.
Jingmin
J
Dong
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D056970:Co-Repressor Proteins / Q000235:genetics; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins; D015854:Up-Regulation / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D056970:Co-Repressor Proteins; C577700:MIRN1246 microRNA, human; C000602308:MIRN1275 microRNA, human; D035683:MicroRNAs; C479077:NKAP protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D003474:Curcumin