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. 2025 Jul 21;20(1):690.
doi: 10.1186/s13018-025-06069-4.

miR-340-5p alleviates the damage effect of LPS on nucleus pulposus cells by negatively regulating the expression of SOX4

Yuhang Liu  1 , Lina Huang  2   3 , Zhengtian Gao  4 , Yingnuo Hou  5 , Fanlei Kong  5 , Shibin Hou  5 , Zheng Li  6
Affiliations

miR-340-5p alleviates the damage effect of LPS on nucleus pulposus cells by negatively regulating the expression of SOX4

Yuhang Liu et al. J Orthop Surg Res. .

Abstract

Background: Previous studies show that about 80% of lumbar disc degeneration (LDD) patients experience back or leg pain, affecting their quality of life. However, the causes of LDD are not fully understood. This study focused on exploring the expression level of miR-340-5p and SRY-related high-mobility-group box 4 (SOX4) in LDD and attempts to clarify its potential mechanism in the pathological process of LDD.

Methods: A total of 88 patients with LDD and 80 non-LDD patients were continuously included in this study. The miR-340-5p levels in nucleus pulposus (NP) tissues were measured using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). The potential diagnostic significance of miR-340-5p for LDD was evaluated by generating a Receiver Operating Characteristic (ROC) curve. The impacts of miR-340-5p on Lipopolysaccharide (LPS)-stimulated NP cells were analyzed through the Cell Counting Kit-8 (CCK-8) method, and apoptosis levels were quantified using flow cytometry. Additionally, the concentrations of inflammatory cytokines and extracellular matrix (ECM) remodeling markers were assessed with Enzyme-Linked Immunosorbent Assay (ELISA) kits.

Results: miR-340-5p was abnormally down-regulated in LDD patients and the ROC curve showed that miR-340-5p has diagnostic value for LDD (AUC = 0.909, sensitivity = 81.8%, specificity = 85.0%, cutoff value = 0.815). Additionally, the enforced expression of miR-340-5p promoted proliferation and ECM remodeling and inhibited the level of apoptosis and pro-inflammatory factors in LPS-damaged NP cells. However, overexpression of SOX4 counteracted the effects of miR-340-5p overexpression on LPS-induced NP cells.

Conclusions: miR-340-5p alleviates the damage effect of LPS on NP cells by negatively regulating the SOX4, and miR-340-5p may be a potential therapeutic target for LDD.

Keywords: Extracellular matrix; Inflammation; Lumbar disc degeneration; SOX4; miR-340-5p.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study has been approved by the ethics committee of Xingtai People’s Hospital, and all patients participating in the study have signed the informed consent form. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Expression level and diagnostic role of miR-340-5p in LDD. ***P<0.001. The expression level of miR-340-5p in Control group (n = 80) and LDD patients (n = 88) (A). The ROC curve of miR-340-5p for diagnosing LDD (B)
Fig. 2
Fig. 2
miR-340-5p negatively regulated the expression of SOX4. ***P<0.001, **P<0.01, ns: no significant difference. The expression level of SOX4 in Control group (n = 80) and LDD patients (n = 88) (A). The correlation between the expression levels of miR-340-5p and SOX4 in patients with LDD (B). The binding site of miR-340-5p and SOX4 (C). The binding relationship between miR-340-5p and SOX4 was verified by the dual-luciferase assay (D). The regulatory effect of miR-340-5p on the expression level of SOX4 (E-F)
Fig. 3
Fig. 3
Effects of miR-340-5p and SOX4 on the proliferation and apoptosis of LPS-induced NP cells. ***P<0.001, **P<0.01, *P<0.05, ns: no significant difference. The expression of miR-340-5p in LPS-induced NP cells (A). The effect of overexpressing miR-340-5p on SOX4 in LPS-induced NP cells (B) The effects of miR-340-5p and SOX4 on LPS-induced cell proliferation (C). The effects of miR-340-5p and SOX4 on LPS-induced cell apoptosis (D)
Fig. 4
Fig. 4
Effects of miR-340-5p and SOX4 on inflammation and ECM remodeling in LPS-induced NP cells. ***P<0.001, **P<0.01, *P<0.05. The effects of miR-340-5p and SOX4 on LPS-induced TNF-α, IL-1β, and IL-6 levels (A-C). The effects of miR-340-5p and SOX4 on the levels of MMP13 (D), Aggrecan (E) and Collagen II (F)
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