MicroRNA-124 involves in ankylosing spondylitis by targeting ANTXR2
MicroRNA-124 involves in ankylosing spondylitis by targeting ANTXR2
复制标题
DOI：
10.3109/14397595.2015.1023887
复制
发表时间：
2015-01-01
影响因子：
2.2
通讯作者：
Zhao, Yue-Ran
中科院分区：
文献类型：
--
作者：
Xia, Yu;Chen, Kun;Zhao, Yue-Ran
目标.最近的一项全基因组关联研究（GWAS）发现炭疽毒素受体2（ANTXR 2）是强直性脊柱炎（AS）的危险位点之一。先前的研究还表明，ANTXR 2可能会影响新骨的形成。本研究旨在探讨ANTXR 2参与AS发病的可能机制。采用实时荧光定量PCR或qRT-PCR检测外周血中ANTXR 2和miR-124的表达水平。TargetScan预测ANTXR 2是miR-124的靶基因，荧光素酶报告基因检测证实了这一点。Western blot分析miR-124对c-Jun N-末端激酶（JNK）活化的影响，并评估自噬的活化状态。我们证实了AS患者外周血中ANTXR 2下调，miR-124上调。有趣的是，miR-124靶向ANTXR 2，并且miR-124在Jurkat细胞中的过表达显著抑制ANTXR 2表达。miR-124抑制ANTXR 2可促进JNK活化并诱导自噬。结果提示，miR-124可能通过靶向ANTXR 2诱导自噬参与AS的发病过程。
Objectives. A recent genome-wide association study or GWAS identified that anthrax roxin receptor 2 (ANTXR2) was one of the risk loci for ankylosing spondylitis (AS). Previous study also showed that ANTXR2 could potentially affect new bone formation. This study aimed to investigate the possible mechanisms of ANTXR2 involved in AS pathogenesis.Methods. The expression level of ANTXR2 and miR-124 in peripheral blood was detected by quantitative real-time polymerase chain reaction or qRT-PCR. ANTXR2 was predicted to be a target gene of miR-124 by TargetScan, which was confirmed by luciferase reporter assays. Western blot analysis was used to further investigate the effect of miR-124 on c-Jun N-terminal kinase (JNK) activation and evaluate the activated status of autophagy.Results. We evidenced that ANTXR2 was downregulated and miR-124 was upregulated in peripheral blood from AS patients. Intriguingly, miR-124 targeted ANTXR2 and overexpression of miR-124 in Jurkat cells notably inhibited ANTXR2 expression. ANTXR2 inhibition by miR-124 promoted JNK activation and induced autophagy.Conclusions. Our results suggested that miR-124 might induce autophagy to participate in AS by targeting ANTXR2, which might be implicated in pathological process of AS.