Analysis of association between MALAT1 haplotype and the severity of normal‐tension glaucoma (NTG)

Autor: Jin-Liang Yue, Shu-Feng Zheng
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.15906
Popis: 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.
Databáze: OpenAIRE