Dataset Information

MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

ABSTRACT: This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM-rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.

SUBMITTER: Rong H

PROVIDER: S-EPMC5689585 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

Rong Han H Gu Shanshan S Zhang Guowei G Kang Lihua L Yang Mei M Zhang Junfang J Shen Xinyue X Guan Huaijin H

Oncotarget 20170503 49

This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifica ...[more]

PMID: 29156695

Similar Datasets

Project description:Developing novel approaches to treat skeletal disorders requires an understanding of how critical molecular factors regulate osteoblast differentiation and bone remodeling. We have reported that (1) retinoic acid receptor-related orphan receptor beta (Ror?) is upregulated in bone samples isolated from aged mice and humans in vivo; (2) Ror? expression is inhibited during osteoblastic differentiation in vitro; and (3) genetic deletion of Ror? in mice results in preservation of bone mass during aging. These data establish that Ror? inhibits osteogenesis and that strict control of Ror? expression is essential for bone homeostasis. Because microRNAs (miRNAs) are known to play important roles in the regulation of gene expression in bone, we explored whether a predicted subset of nine miRNAs regulates Ror? expression during both osteoblast differentiation and aging. Mouse osteoblastic cells were differentiated in vitro and assayed for Ror? and miRNA expression. As Ror? levels declined with differentiation, the expression of many of these miRNAs, including miR-219a-5p, was increased. We further demonstrated that miR-219a-5p was decreased in bone samples from old (24-month) mice, as compared with young (6-month) mice, concomitant with increased Ror? expression. Importantly, we also found that miR-219a-5p expression was decreased in aged human bone biopsies compared with young controls, demonstrating that this phenomenon also occurs in aging bone in humans. Inhibition of miR-219a-5p in mouse calvarial osteoblasts led to increased Ror? expression and decreased alkaline phosphatase expression and activity, whereas a miR-219a-5p mimic decreased Ror? expression and increased osteogenic activity. Finally, we demonstrated that miR-219a-5p physically interacts with Ror? mRNA in osteoblasts, defining Ror? as a true molecular target of miR-219a-5p. Overall, our findings demonstrate that miR-219a-5p is involved in the regulation of Ror? in both mouse and human bone. © 2018 American Society for Bone and Mineral Research.

Dataset Information

MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

Publications

MiR-2964a-5p binding site SNP regulates <i>ATM</i> expression contributing to age-related cataract risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets