Identification of circ-FAM169A sponges miR-583 involved in the regulation of intervertebral disc degeneration.
Identification of circ-FAM169A sponges miR-583 involved in the regulation of intervertebral disc degeneration.
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circ-FAM169A海绵miR-583参与椎间盘退变调节的鉴定
DOI:
10.1016/j.jot.2020.07.007
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发表时间:
2021-01
影响因子:
6.6
通讯作者:
Feng S
中科院分区:
文献类型:
--
作者:
Li Y;Pan D;Liu S;Xing X;Zhou H;Zhang B;Zhang D;Li B;Li G;Tao B;Ning G;Feng S
Low back pain (LBP) is the predominant cause of disc degeneration in patients, which brings serious social problems and economic burdens. Increasing evidence has indicated that intervertebral disc degeneration (IDD) is one of the most common causes triggering LBP. Accumulating evidence has shown that circRNAs are involved in the pathological process of IDD. Nevertheless, the circRNA-mediated IDD pathogenesis still remains unknown. This study explored the potential mechanism and functions of circ-FAM169A in NPCs. Bioinformatics analysis was conducted to identify key circRNA, miRNA and mRNA and predict their potential role in IDD. Dual-luciferase reporter assay, western blot, qRT-PCR, and fluorescence in situ hybridisation (FISH) were used to demonstrate the interaction among circ-FAM169A, miR-583 and Sox9 in NPCs. Herein, we identified circ-FAM169A, which was dramatically up-regulated in degenerative nucleus pulposus (NP) tissues and negatively correlated with expression levels of miR-583. We constructed a circ-FAM169A-miR-583-mRNAs co-expression network and predicted circ-FAM169A-miR-583 pathway predominantly involved in extracellular matrix metabolism and cell apoptosis etc. FISH experiments confirmed circ-FAM169A and miR-583 co-existence in the cytoplasm of NPCs. Luciferase reporter assay illustrated that circ-FAM169A was directly bound to miR-583 and Sox9 was the directly target gene of miR-583. Additionally, miR-583 negatively regulated Sox9 mRNA and protein levels in NPCs. Findings of this study indicated that circ-FAM169A-miR-583 pathway may play a significant role in the regulation of IDD, which will provide novel diagnostic biomarkers and develop effective treatment strategy of IDD diseases. This study suggested that circ-FAM169A-miR-583 pathway may regulate NPCs apoptosis and extracellular matrix synthesis and catabolism by targeting Sox9. It provides a novel therapeutic target and strategy for IVDD diseases.
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DOI:
10.1016/s0140-6736(18)32203-7
发表时间:
2018-11-10
期刊:
Lancet (London, England)
影响因子:
--
作者:
GBD 2017 Causes of Death Collaborators
通讯作者:
GBD 2017 Causes of Death Collaborators
DOI:
10.1038/nrrheum.2013.160
发表时间:
2014-01
期刊:
Nature reviews. Rheumatology
影响因子:
--
作者:
通讯作者:
--
影响因子:
9
作者:
Guo W;Zhang B;Mu K;Feng SQ;Dong ZY;Ning GZ;Li HR;Liu S;Zhao L;Li Y;Yu BB;Duan HQ;Sun C;Li YJ
通讯作者:
Li YJ
影响因子:
6.8
作者:
Feng, Yi;Egan, Brian;Wang, Jinxi
通讯作者:
Wang, Jinxi
影响因子:
27.4
作者:
Cheng X;Zhang L;Zhang K;Zhang G;Hu Y;Sun X;Zhao C;Li H;Li YM;Zhao J
通讯作者:
Zhao J