MicroRNA-124 involves in ankylosing spondylitis by targeting ANTXR2

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Ankylosing spondylitis (AS) is a chronic inflammatory disease.
• Genome-wide association studies (GWAS) identified anthrax toxin receptor 2 (ANTXR2) as a risk locus for AS.
• ANTXR2 has been previously linked to new bone formation, a key feature of AS.

Purpose of the Study:

• To investigate the molecular mechanisms by which ANTXR2 is involved in the pathogenesis of AS.
• To explore the relationship between ANTXR2 and microRNA-124 (miR-124) in AS.
• To elucidate the downstream signaling pathways affected by ANTXR2 modulation in AS.

Main Methods:

• Quantitative real-time polymerase chain reaction (qRT-PCR) to measure ANTXR2 and miR-124 expression in peripheral blood of AS patients.
• Luciferase reporter assays to confirm the targeting of ANTXR2 by miR-124.
• Western blot analysis to assess c-Jun N-terminal kinase (JNK) activation and autophagy status.

Main Results:

• ANTXR2 expression was significantly downregulated, while miR-124 expression was upregulated in peripheral blood from AS patients.
• miR-124 directly targets and inhibits ANTXR2 expression, as confirmed by luciferase assays and overexpression studies.
• Inhibition of ANTXR2 by miR-124 led to increased JNK activation and induced autophagy.

Conclusions:

• miR-124 plays a role in AS pathogenesis by targeting ANTXR2.
• The miR-124/ANTXR2 axis promotes JNK activation and induces autophagy, contributing to the pathological processes in AS.
• This study reveals a novel molecular mechanism implicating miR-124 and ANTXR2 in AS development.