Journal of neurosurgery. Spine · 2026
Targeting EGFR with miR-148a-3p: a novel approach to mitigate intervertebral disc degeneration.
СтатьяНазвание и аннотация: Перевод в очереди
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Zhang Lei, Cong Xiaoming, Sun Shaowei, Li Pengcheng, Zhao Wei, Wang Nan, Shen Dewei, Zhang Yang
Аннотация
OBJECTIVE: In light of microRNA (miRNA)-targeted therapies in the management of intervertebral disc degeneration (IVDD), this study aimed to elucidate the role and mechanism of miRNA (miR)-148a-3p in the pathogenesis of IVDD.
METHODS: Human nucleus pulposus (NP) cells treated with interleukin (IL)-1β (10 ng/mL) were used to simulate IVDD in vitro. Gain-of-function experiments were performed by transfecting NP cells with an miR-148a-3p mimic and a pcDNA-epidermal growth factor receptor (EGFR) vector (a mammalian expression encoding EGFR) and evaluated using the CCK-8 assay and TUNEL staining. The target of miR-148a-3p was identified by a dual-luciferase reporter assay. An in vivo IVDD model was established using Sprague-Dawley rats subjected to acupuncture, followed by histological, inflammatory, and expression analyses.
RESULTS: Downregulation of miR-148a-3p but upregulation of EGFR was observed in IL-1β-treated NP cells. Increasing miR-148a-3p resulted in elevated cell viability but decreased apoptosis in IL-1β-treated NP cells. Meanwhile, the upregulation of miR-148a-3p effectively counteracted all IL-1β-induced alterations in protein expression, as demonstrated by the enhanced expression of extracellular matrix (ECM)-associated markers, alongside a reduction in autophagy markers such as LC3II/LC3I, Beclin1, and ATG7. MiR-148a-3p was found to exert a negative regulatory effect on EGFR. The overexpression of EGFR negated the alterations induced by the miR-148a-3p mimic. In the IVDD rat model, miR-148a-3p ameliorated histological damage and enhanced ECM marker expression while concurrently reducing the inflammatory response and autophagy markers.
CONCLUSIONS: The restoration of miR-148a-3p inhibited EGFR, thereby suppressing inflammation, apoptosis, and autophagy but promoting ECM production in IVDD models. Therefore, miR-148a-3p may serve as a potential therapeutic candidate for the management of IVDD.
METHODS: Human nucleus pulposus (NP) cells treated with interleukin (IL)-1β (10 ng/mL) were used to simulate IVDD in vitro. Gain-of-function experiments were performed by transfecting NP cells with an miR-148a-3p mimic and a pcDNA-epidermal growth factor receptor (EGFR) vector (a mammalian expression encoding EGFR) and evaluated using the CCK-8 assay and TUNEL staining. The target of miR-148a-3p was identified by a dual-luciferase reporter assay. An in vivo IVDD model was established using Sprague-Dawley rats subjected to acupuncture, followed by histological, inflammatory, and expression analyses.
RESULTS: Downregulation of miR-148a-3p but upregulation of EGFR was observed in IL-1β-treated NP cells. Increasing miR-148a-3p resulted in elevated cell viability but decreased apoptosis in IL-1β-treated NP cells. Meanwhile, the upregulation of miR-148a-3p effectively counteracted all IL-1β-induced alterations in protein expression, as demonstrated by the enhanced expression of extracellular matrix (ECM)-associated markers, alongside a reduction in autophagy markers such as LC3II/LC3I, Beclin1, and ATG7. MiR-148a-3p was found to exert a negative regulatory effect on EGFR. The overexpression of EGFR negated the alterations induced by the miR-148a-3p mimic. In the IVDD rat model, miR-148a-3p ameliorated histological damage and enhanced ECM marker expression while concurrently reducing the inflammatory response and autophagy markers.
CONCLUSIONS: The restoration of miR-148a-3p inhibited EGFR, thereby suppressing inflammation, apoptosis, and autophagy but promoting ECM production in IVDD models. Therefore, miR-148a-3p may serve as a potential therapeutic candidate for the management of IVDD.