Abstract
MALAT1, which is disorderly expressed in the growth, invasion, migration and cancer cell apoptosis, was shown to be associated with normal‐tension glaucoma (NTG), a type of optic neuropathy. The haplotype in MALAT1 affects its expression and is correlated with human diseases like normal‐tension glaucoma (NTG). However, the underlying detailed mechanism remains unclear. In this study, we aimed to analyse the association between MALAT1 haplotype and the severity of NTG in a molecular level. Quantitative real‐time PCR, ELISA and luciferase assays were performed to establish the underlying signalling pathways. RNFL thickness, RA and C/D ratio were calculated for NTG patients. Accordingly, GGGT haplotype was demonstrated to be associated with a decreased risk of NTG. The MALAT1 level in serum of NTG patients carrying GGGT haplotype was significantly decreased compared with NTG patients carrying other haplotypes, along with elevated miR‐1 expression and diminished IL‐6 expression. NTG patients carrying GGGT haplotype had thicker RNFL and RA, but a smaller C/D ratio. Sequence analysis found potential target sites of miR‐1 on MALAT1 and IL‐6, and luciferase assay confirmed the inhibitory effect of miR‐1 on MALAT1 and IL‐6 expression. Meanwhile, MALAT1 also down‐regulated miR‐1 expression and consequently up‐regulated IL‐6 expression. This study presented evidence for a regulatory network containing MALAT1, miR‐1 and IL‐6, and further demonstrated the effect of MALAT1 haplotype on the risk and severity of NTG.
Highlights
The haplotype in MALAT1 affects its expression and is correlated with human diseases like Normal Tension Glaucoma (NTG), its detailed mechanism remains unclear
Compared to the other haplotypes, the GGGT haplotype was associated with a decreased risk of normal tension glaucoma (NTG) (P < 0.001), while other five haplotypes were not associated with the risk of NTG (P > 0.05)
It was demonstrated that the protective role of MALAT1 in glaucoma patients is played via the PI3K/Akt cascade to reduce the apoptosis of RGCs [26]
Summary
The haplotype in MALAT1 affects its expression and is correlated with human diseases like Normal Tension Glaucoma (NTG), its detailed mechanism remains unclear. As a type of optic neuropathy, normal tension glaucoma (NTG) does not cause abnormal intraocular pressure (IOP) in its patients. Single nucleotide polymorphism (SNP) in IL-6 was demonstrated to be involved in glaucoma pathogenesis in patients with NTG. The effect of IL-6 SNP on NTG may be caused by the close relationship between the level of IL-6 and neurodegenerative disorders. The SNPs in IL-6 were implicated in a wide range of human disorders by altering the level of IL-6 expression [10]. A G/C SNP located in the promoter of IL-6 can affect the serum expression of IL-6 as well as the transcription of IL-6 DNA. Fishman et al showed that the concentration of serum IL-6 in subjects carrying the GG genotype of this SNP was twice that in subjects carrying the C allele of this SNP [11]
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