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

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.