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

Author:

Guo Wei,Mu Kun,Zhang Bin,Sun Chao,Zhao Ling,Li Hao-Ran,Dong Zhan-Yin,Cui Qing

Abstract

AbstractIntervertebral 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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Hebei Province

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

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