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EIF4A3-Induced Upregulation of hsa_circ_0040039 is a Biomarker and Aggravates IL-1β-Stimulated Intervertebral Disc Degeneration

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Abstract

Intervertebral disc degeneration (IDD) is characterised by nucleus pulposus (NP) loss and extracellular matrix (ECM) degeneration. Circular RNAs (circRNAs) have been reported to be dysregulated during IDD progression. Recently, reports showed that hsa_circ_0040039 was increased in degenerated lumbar disc samples. The aim of this study was to explore the specific role and underlying mechanisms of hsa_circ_0040039 in IDD. The expression of hsa_circ_0040039 was investigated in NP tissues of IDD patients. IL-1β was used to treat NP cells to construct an IDD in vitro model. Overexpression and loss-of-function assays and bioinformatic analysis were performed to evaluate the role and potential mechanism of hsa_circ_0040039 during IDD progression. Hsa_circ_0040039 expression was increased about 2 folds in NP tissues compared with normal tissues and IL-1β-stimulated NP cells also presented hsa_circ_0040039 upregulation, and its overexpression promoted cell proliferation and ECM degeneration. The depletion of hsa_circ_0040039 had the opposite effects. Based on bioinformatics prediction, Luciferase assay, PCR and Western blot, our study verified that hsa_circ_0040039 directly bond to miR-146b-3p, then mediated its targeted MMP2 and PCNA. Moreover, the overexpression of miR-146b-3p and the silence of MMP2 or PCNA, partially abolished the effect of hsa_circ_0040039 on IL-1β-stimulated NPs. Hsa_circ_0040039 may participate in IDD development by mediating the repair and regeneration of NPs through upregulation MMP2 and PCNA mediated by miR-146b-3p.

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Data Availability

The data supporting the conclusions of this article are included within the article.

Abbreviations

IDD :

Intervertebral disc degeneration

NP :

Nucleus pulposus

ECM :

Extracellular matrix

IL-1β :

Interleukin-1β

MMPs :

Matrix metalloproteinases

HNPCs :

Human nucleus pulposus cells

ov-circ :

Overexpression vector of hsa_circ_0040039

eIF4A3 :

Eukaryotic translation initiation factor 4A3

PCNA :

Proliferating cell nuclear antigen

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Funding

This work was supported by Key Research and Development Program of Shaanxi (2023-YBSF-617).

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    Authors and Affiliations

    1. Department of Traditional Chinese Medicine Orthopedics Diagnosis and Treatment Center, Honghui Hospital, Xi’an Jiaotong University, No. 555, Friendship East Road, Beilin District, 710054, Xi’an, Shaanxi, China

      Liang Li, Yi Cao & Xiaochen Fan

    2. Department of Soft Tissue Injury, Nanchang Hongdu Hospital of Traditional Chinese Medicine, 330006, Nanchang, Jiangxi, China

      Haidong Deng

    3. Health Administrative Center, Xi’an Fourth Hospital, 710004, Xi’an, Shaanxi, China

      Jing Jia

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    Contributions

    Xiaochen Fan contributed to the conception of the study; Yi Cao and Haidong Deng performed the experiment; Jing Jia contributed significantly to analysis and manuscript preparation; Liang Li performed the data analyses and wrote the manuscript; Xiaochen Fan helped perform the analysis with constructive discussions.

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    Correspondence to Xiaochen Fan.

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    Li, L., Cao, Y., Deng, H. et al. EIF4A3-Induced Upregulation of hsa_circ_0040039 is a Biomarker and Aggravates IL-1β-Stimulated Intervertebral Disc Degeneration. Appl Biochem Biotechnol 195, 4292–4307 (2023). https://doi.org/10.1007/s12010-023-04334-y

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