miR-302a-3p mitigates intervertebral disc degeneration progression through regulating EPHA2

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• The molecular underpinnings of intervertebral disc degeneration (IDD) require further elucidation.
• Identifying novel molecular targets is crucial for developing effective therapeutic strategies for IDD.

Purpose of the Study:

• To investigate the role of microRNA-302a-3p (miR-302a-3p) in the pathogenesis of IDD.
• To explore the regulatory mechanism of miR-302a-3p in IDD, focusing on its interaction with EPHA2.

Main Methods:

• Expression analysis of miR-302a-3p and EPHA2 in IDD patients versus healthy controls using RT-qPCR.
• Establishment of a lipopolysaccharide (LPS)-induced nucleus pulposus (NP) cell injury model.
• Assessment of cell proliferation, apoptosis, inflammatory cytokine levels (TNF-α, IL-1β), and direct targeting via dual-luciferase reporter assays.

Main Results:

• miR-302a-3p expression was significantly decreased in IDD patients and showed diagnostic potential.
• In LPS-induced NP cells, reduced miR-302a-3p correlated with decreased proliferation, increased apoptosis, and elevated inflammatory markers.
• Overexpression of miR-302a-3p ameliorated these detrimental effects, while EPHA2, a direct target, was upregulated in IDD and partially reversed miR-302a-3p's protective actions.

Conclusions:

• miR-302a-3p acts as a protective factor in IDD by suppressing inflammation and apoptosis.
• The therapeutic potential of targeting the miR-302a-3p/EPHA2 axis for IDD treatment warrants further investigation.