Circ_0040039 May Aggravate Intervertebral Disk Degeneration by Regulating the MiR-874-3p-ESR1 Pathway

Yongjin Li; Xuke Wang; Haiwei Xu; Guowang Li; Zhenxin Huo; Lilong Du; Kaihui Zhang; Li Shen; Hao Li; Baoshan Xu

doi:10.3389/fgene.2021.656759

Circ_0040039 May Aggravate Intervertebral Disk Degeneration by Regulating the MiR-874-3p-ESR1 Pathway

Front Genet. 2021 Jun 11:12:656759. doi: 10.3389/fgene.2021.656759. eCollection 2021.

Authors

Yongjin Li^{1

2

3}, Xuke Wang^{2

4}, Haiwei Xu², Guowang Li^{1

2

3}, Zhenxin Huo^{1

2

3}, Lilong Du^{1

2

3}, Kaihui Zhang^{1

2

3}, Li Shen^{1

2

3}, Hao Li^{1

2

3}, Baoshan Xu^{1

2

3}

Affiliations

¹ Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin, China.
² Graduate School, Tianjin Medical University, Tianjin, China.
³ Tianjin Hospital, Orthopedic Research Institute, Tianjin, China.
⁴ Department of Minimally Invasive Spine Surgery, Luoyang Orthopedic- Traumatological Hospital, Luoyang, China.

Abstract

The functional alteration of nucleus pulposus cells (NPCs) exerts a crucial role in the occurrence and progression of intervertebral disk degeneration (IDD). Circular RNAs and microRNAs (miRs) are critical regulators of NPC metabolic processes such as growth and apoptosis. In this study, bioinformatics tools, encompassing Gene Ontology pathway and Venn diagrams analysis, and protein-protein interaction (PPI) network construction were used to identify functional molecules related to IDD. PPI network unveiled that ESR1 was one of the most critical genes in IDD. Then, a key IDD-related circ_0040039-miR-874-3p-ESR1 interaction network was predicted and constructed. Circ_0040039 promoted miR-874-3p and repressed ESR1 expression, and miR-874-3p repressed ESR1 expression in NPCs, suggesting ESR1 might be a direct target of miR-874-3p. Functionally, circ_0040039 could enhance NPC apoptosis and inhibit NPC growth, revealing that circ_0040039 might aggravate IDD by stabilizing miR-874-3p and further upregulating the miR-874-3p-ESR1 pathway. This signaling pathway might provide a novel therapeutic strategy and targets for the diagnosis and therapy of IDD-related diseases.

Keywords: ESR1; apoptosis; circular RNA; intervertebral disk degeneration; miR-874-3p.