机构：[1]Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China昆明医科大学附属第一医院[2]Department of Orthopedics, The First People’s Hospital of Yunnan, Kunming 650032, Yunnan, China.
Long noncoding RNAs (lncRNAs) are critical regulators of gene transcription. Our previous results have demonstrated that iron deficiency accelerates intervertebral disc degeneration (IDD) by affecting the stability of the DNA polymerase epsilon (Polε) complex. Here, we discovered that the novel lncRNA lncPolE functions as a negative regulator of Polε. The expression of lncPolE in IDD tissues was upregulated compared to its expression in healthy control tissues, and this was in contrast to the PolE1 expression levels. The increased lncPolE level was significantly correlated with the severity of IDD. Ectopic expression of lncPolE in human nucleus pulposus cells (hNPCs) was able to decrease PolE1 levels and cause apoptosis, while the specific knockdown of lncPolE in primary NP cells (pNPCs) from IDD patients can restore PolE1 levels. Interestingly, iron depletion or supplementation can affect the expression of lncPolE. Further analyses indicated that the downregulation of DNA methylation in the promoter region of lncPolE caused its overexpression. Collectively, our results suggest that the aberrant expression of lncPolE contributes to the pathogenesis of IDD by negatively regulating PolE1 in iron deficient conditions, and this may provide a new avenue to alleviate IDD progression in clinical treatment.
基金：
This study was supported by a grant from the
National Natural Science Foundation of China (No. 81601939) and two grants from Yunnan
Applied Basic Research Projects (No. 2017FE-
468-145 and No. 2018FB125).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区医学
小类|3 区医学：研究与实验4 区肿瘤学
最新[2023]版：
大类|4 区医学
小类|4 区医学：研究与实验4 区肿瘤学
第一作者：
第一作者机构：[1]Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China[2]Department of Orthopedics, The First People’s Hospital of Yunnan, Kunming 650032, Yunnan, China.[*1]Department of Orthopedics, The First People’s Hospital of Yunnan, Kunming 650032, Yunnan, China.[*2]Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
推荐引用方式(GB/T 7714)：
Xingguo Li,Zhenkai Lou,Jie Liu,et al.Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon.[J].American journal of translational research.2019,11(5):2843-2854.
APA：
Xingguo Li,Zhenkai Lou,Jie Liu,Hongkun Li,Yu Lei...&Fan Zhang.(2019).Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon..American journal of translational research,11,(5)
MLA：
Xingguo Li,et al."Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon.".American journal of translational research 11..5(2019):2843-2854
