MicroRNA-328 may influence myopia development by mediating the PAX6 gene.

Ku Chung Chen, Edward Hsi, Ching Yu Hu, Wen Wen Chou, Chung Ling Liang, Suh Hang Hank Juo

研究成果: 雜誌貢獻文章同行評審

45 引文 斯高帕斯(Scopus)

摘要

We showed previously that single nucleotide polymorphism (SNP) rs662702 in PAX6 may be located in a microRNA-328 binding site that causes susceptibility to high myopia. Our study was done to elucidate the role of PAX6 and its relationship with microRNA-328 in myopia. A luciferase assay was used to confirm microRNA-328 binding to the PAX6 locus. Clones containing each allele of rs662702 were created and tested for their binding affinity to microRNA-328. Because a low level of PAX6 is a risk factor for myopia, we tested whether knockdown of PAX6 affects retinal pigment epithelial (RPE) cells and scleral cells, as well as expression of myopia-related genes. We also tested for the effect of retinoic acid (RA) on microRNA-328 expression, since RA-responsive elements are predicted to lie in the microRNA-328 promoter. MicroRNA-328 was shown to bind to the wild-type, but not mutant 3' untranslated region (UTR) of PAX6. The risk C allele of rs644242 had strong response to microRNA-328 but the protective T allele did not respond to microRNA-328. Down-regulation of PAX6 in RPE increased RPE proliferation, but reduced scleral cell proliferation. In addition, transforming growth factor (TGF)-β3 in the RPE and matrix malleoproteinase-2 (MMP2) in the sclera were increased, while collagen I and integrin β1 in the sclera were decreased. RA dose-dependently increased microRNA-328 expression and, in turn, suppressed PAX6 expression. We elaborated the relationship among myopia development, SNP rs662702, microRNA-328 and RA. The data imply that reduction of miR-328 and/or RA can be potential strategies for myopia prevention or treatment.

原文英語
頁(從 - 到)2732-2739
頁數8
期刊Investigative Ophthalmology and Visual Science
53
發行號6
出版狀態已發佈 - 五月 2012
對外發佈

ASJC Scopus subject areas

  • 醫藥 (全部)

指紋

深入研究「MicroRNA-328 may influence myopia development by mediating the PAX6 gene.」主題。共同形成了獨特的指紋。

引用此