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The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration.

ABSTRACT: Intervertebral disc degeneration (IDD) is the most common degenerative disease all over the word. Our previous study confirmed that the downregulated circ-GRB10 directly interacts with miR-328-5p, which modulate ERBB2 and leads to the degeneration of intervertebral disc; however, the underpinning mechanism of circ-GRB10 dysregulation remains unclear. We identified that FUS and demonstrated that circ-GBR10 biosynthesis in nucleus pulposus (NP) cells was promoted by FUS, whose expression was controlled by miR-141-3p. In addition, ERBB2 downregulation led to decreased Erk1/2 phosphorylation which enhanced miR-141-3p production in NP cells. In vivo data indicated that circ-GRB10 inhibited IDD in rat model. The present study revealed that miR-141-3p and FUS are key factors that regulate circ-GRB10 synthesis in NP cells. In addition, circ-GBR10 participates in the molecular circuitry that controls human IDD development. These findings provide a basis for further functional, diagnostic and therapeutic studies of circ-GRB10 in IDD.

SUBMITTER: Guo W

PROVIDER: S-EPMC7426430 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration.

Guo Wei W Mu Kun K Zhang Bin B Sun Chao C Zhao Ling L Li Hao-Ran HR Dong Zhan-Yin ZY Cui Qing Q

Cell death & disease 20200813 8

Intervertebral disc degeneration (IDD) is the most common degenerative disease all over the word. Our previous study confirmed that the downregulated circ-GRB10 directly interacts with miR-328-5p, which modulate ERBB2 and leads to the degeneration of intervertebral disc; however, the underpinning mechanism of circ-GRB10 dysregulation remains unclear. We identified that FUS and demonstrated that circ-GBR10 biosynthesis in nucleus pulposus (NP) cells was promoted by FUS, whose expression was contr ...[more]

PMID: 32792505

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Project description:Summary Objective Low back pain (LBP) is the predominant cause of disc degeneration in patients, which brings serious social problems and economic burdens. Increasing evidence has indicated that intervertebral disc degeneration (IDD) is one of the most common causes triggering LBP. Accumulating evidence has shown that circRNAs are involved in the pathological process of IDD. Nevertheless, the circRNA-mediated IDD pathogenesis still remains unknown. This study explored the potential mechanism and functions of circ-FAM169A in NPCs. Methods Bioinformatics analysis was conducted to identify key circRNA, miRNA and mRNA and predict their potential role in IDD. Dual-luciferase reporter assay, western blot, qRT-PCR, and fluorescence in situ hybridisation (FISH) were used to demonstrate the interaction among circ-FAM169A, miR-583 and Sox9 in NPCs. Results Herein, we identified circ-FAM169A, which was dramatically up-regulated in degenerative nucleus pulposus (NP) tissues and negatively correlated with expression levels of miR-583. We constructed a circ-FAM169A-miR-583-mRNAs co-expression network and predicted circ-FAM169A-miR-583 pathway predominantly involved in extracellular matrix metabolism and cell apoptosis etc. FISH experiments confirmed circ-FAM169A and miR-583 co-existence in the cytoplasm of NPCs. Luciferase reporter assay illustrated that circ-FAM169A was directly bound to miR-583 and Sox9 was the directly target gene of miR-583. Additionally, miR-583 negatively regulated Sox9 mRNA and protein levels in NPCs. Conclusion Findings of this study indicated that circ-FAM169A-miR-583 pathway may play a significant role in the regulation of IDD, which will provide novel diagnostic biomarkers and develop effective treatment strategy of IDD diseases. The translational potential of this article This study suggested that circ-FAM169A-miR-583 pathway may regulate NPCs apoptosis and extracellular matrix synthesis and catabolism by targeting Sox9. It provides a novel therapeutic target and strategy for IVDD diseases.

Dataset Information

The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration.

Publications

The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration.

Similar Datasets

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