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miR-302a-3p mitigates intervertebral disc degeneration progression through regulating EPHA2
Weihan Qu1, Laicong Liao2, Ganggang Wang3
1Orthopaedic Department, Peking University Third Hospital Qinhuangdao Hospital, Qinhuangdao, 066000, China.
Background:
Intervertebral disc degeneration (IDD) underlying molecular mechanisms remain incompletely understood.
Objectives:
To explore the role of miR-302a-3p in IDD and elucidate its targeted regulatory mechanism.
Methods:
130 IDD patients and 130 healthy controls were collected. The miR-302a-3p and EPHA2 expressions were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). A lipopolysaccharide (LPS)-induced cell injury model was established using human nucleus pulposus (NP) cells. Proliferation was assessed using the cell counting kit-8 (CCK-8) assay, apoptosis was determined by flow cytometry, and the concentrations of inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). A dual-luciferase reporter gene assay was conducted to confirm the targeted regulatory interaction.
Results:
miR-302a-3p expression was significantly decreased in IDD patients (P < 0.001), and receiver operating characteristic (ROC) curve analysis indicated that it possessed certain diagnostic potential (P < 0.001, AUC = 0.8808, 95% confidence interval (CI) = 0.8400-0.9216). In the LPS-induced NP cell injury model, miR-302a-3p expression was down-regulated, which was accompanied by reduced cell proliferation, increased apoptosis, and elevated tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) secretion (P < 0.001). However, overexpression of miR-302a-3p could effectively alleviate these injury-related effects. Furthermore, miR-302a-3p directly targeted EPHA2, whose expression was up-regulated in IDD (P < 0.001). Overexpression of EPHA2 partially reversed the protective effects of miR-302a-3p on cell proliferation, apoptosis, and inflammatory responses (P < 0.001).
Conclusion:
miR-302a-3p significantly mitigated inflammatory responses and suppressed cell apoptosis by directly targeting and downregulating EPHA2 expression, thereby delaying the progression of IDD.
Insights
MicroRNA-302a-3p, a key regulator, shows reduced levels in intervertebral disc degeneration (IDD). Restoring miR-302a-3p alleviates IDD progression by targeting EPHA2, reducing inflammation and apoptosis.
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.
