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.
Keywords: IL-6; MALAT1; MI-RNA; NTG.
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.