MicroRNA-124 involves in ankylosing spondylitis by targeting ANTXR2.
OBJECTIVE
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.
a Department of Central Laboratory , Shandong Provincial Hospital affiliated to Shandong University , Jinan , China.
Yu
Y
Xia
Kun
K
Chen
Ming-Hua
MH
Zhang
Lai-Cheng
LC
Wang
Chun-Yan
CY
Ma
Yan-Liang
YL
Lin
Yue-Ran
YR
Zhao
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
C447150:ANTXR2 protein, human; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D018000:Receptors, Peptide; D004247:DNA
ANTXR2; Ankylosing Spondylitis; Autophagy; JNK; miR-124