MicroRNA-328 May Influence Myopia Development by Mediating the<i>PAX6</i>Gene

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

doi:10.1167/iovs.11-9272

Cited by 69 publications

(59 citation statements)

References 27 publications

(36 reference statements)

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“…As expected, miR-335 overexpression significantly downregulated the protein expression of PAX6, while inhibition of miR-335 promoted the protein level of PAX6 in U87 and U251 cells, which are WHO IV grade. In fact, several other miRNAs have also been reported to directly target PAX6, including miR-290-295, miR-365-3p and miR-328 (29)(30)(31). Huang et al demonstrated that miR-223 promoted the growth and invasion of glioblastoma cells by targeting PAX6 (32).…”

Section: Discussionmentioning

confidence: 99%

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Cheng

Cao²,

Chen

et al. 2014

Molecular Medicine Reports

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Abstract. Paired box 6 (PAX6), a highly conserved transcription factor, is important in glioma. However, the molecular mechanisms involved remain unclear. The present study demonstrated that the expression of PAX6 was significantly reduced with the malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)-335, which was significantly upregulated in glioma. The inhibition of miR-335 increased the protein expression of PAX6, whereas the upregulation of miR-335 suppressed its expression in human glioma U251 and U87 cells. Furthermore, upregulation of miR-335 promoted U251 cell proliferation, colony formation and invasion, which was reversed by the overexpression of PAX6. Furthermore, the present study demonstrated that the effect of miR-335 on U251 cell invasion was via the modulation of matrix metalloproteinase (MMP)-2 and MMP-9 expression by targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a novel target of miR-335, has an anti-oncogenic function in glioma, and thus PAX6 may serve as a therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 99%

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Cheng

Cao²,

Chen

et al. 2014

Molecular Medicine Reports

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“…36 Our recent study also indicated that TGF-b signaling could play a role in the development of myopia. 29 Hence, FGF10 is likely to have involved in the development of myopia by mediating TGF-b signaling to further remodel ECM.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28] In our previous study of microRNA-328, retinoic acid, and TGF-b were shown to be involved in the same network regulation leading to the development of myopia. 29 A recent study indicated that retinoic acid could regulate the TGFb pathway in the control of FGF10 expression. 30 Therefore, the present study focuses on the involvement of FGF10 in the development of myopia.…”

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confidence: 99%

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Hsi

Chen

Chang

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. METHODS.The expression levels of FGF10 gene were compared among the form deprivation myopic (FDM) eyes, the fellow eyes of the FDM group, and the healthy eyes of experimental mice. In the present study 1020 cases ( À6.0 diopters [D]) and 960 controls ( ‡À1.5 D) were enrolled from a Chinese population. Eight tagging SNPs were genotyped to test for an association between genotypes and myopia. The luciferase reporter assay was conducted for the particular SNP to assess the allelic effect on gene expression. RESULTS.The sclera of FDM eyes had a 2.57-fold higher level of FGF10 mRNA (P ¼ 0.018) than the fellow eyes. Although no SNP was associated with high myopia, SNP rs339501 was significantly associated with extreme myopia ( À10 D, P ¼ 0.008) and the odds ratio (OR) was 1.58 for G allele carriers. The luciferase assay showed that the risk G allele significantly caused a higher expression level than the A allele (P ¼ 0.011).CONCLUSIONS. The evidence suggested FGF10 to be a risk factor for myopia. The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. It is concluded that the FGF10 could have been involved in the development of myopia.Keywords: FDM, myopia, FGF10 M yopia is a common eye condition worldwide, and its prevalence varies widely among populations and ages and between the sexes.1-3 When the definition of less than À6 diopters (D) was used, the prevalence of high myopia was found to be 18% among young Taiwanese men and 24% among young Taiwanese women 1 ; both of which are higher than the 13.1% reported among young men in Singapore.2 Furthermore, an increased frequency of high myopia (<À6.0 D) was found in young Taiwanese people: 10.9% in 1983 and 21% in 2000. 4 Myopia progresses quickly in childhood, especially around the teenage years. By early adulthood, the rate of change in ocular refraction tends to decline and the prevalence of myopia stabilizes. 5 Several studies have also shown the family history of myopia to be a significant risk factor. 6,7 Recently, genetic association studies including genome-wide association studies (GWAS) have reported several susceptibility genes to nonsyndromic myopia. 8-17Scleral remodeling is one of the important mechanisms for the development of myopia, 18 Several genes are associated with the scleral remodeling including sulfated glycosaminoglycans (GAGs), 19 matrix metalloproteinases (MMPs), 20 tissue inhibitors of metalloproteinases (TIMPs), 20 and TGF-b. 21 The expression of fibroblast growth factor 10 (FGF10) has been shown to be abundant in the murine retina and sclera. 22,23 FGF10 plays a pivotal role in controlling elongation of lacrima...

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“…A study from Taiwan revealed that miRNA may play a role in the regulation of the PAX6 gene [29]. miR-328 was predicted to bind to 3′-UTRs of PAX6 transcripts.…”

Section: Mirnas and Eye Disordersmentioning

confidence: 99%

Micro-RNAs and Their Roles in Eye Disorders

Raghunath¹,

Perumal²

2015

Ophthalmic Res

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Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders.

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MicroRNA-328 May Influence Myopia Development by Mediating thePAX6Gene

Abstract: 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.

Cited by 69 publications

References 27 publications

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Micro-RNAs and Their Roles in Eye Disorders

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