Upregulated miR-154 promotes ECM degradation in intervertebral disc degeneration

Intervertebral disc degeneration (IDD), a common global health issue, is a major cause for low back pain (LBP). Given the complex etiology of IDD, micro RNA (miRNA) recently has been demonstrated to play essential roles in the progression of IDD. Therefore, this study aims to investigate functions of the miR-154, which is well-documented in a series of cell activities, IDD, and other relevant mechanisms. Lumbar nucleus pulposus (NP) samples were collected from patients with IDD and the control group. After solexa sequencing and bioinformatical analysis, the results showed that miR-154 was increased in NP cells of patients with IDD. Inhibition of miR-154 increased type II collagen and aggrecan and decreased mRNA expressions of collagenase-3 (MMP13) and aggrecanase-1 (ADAMTS4), whereas overexpression of miR-154 reversed such effects in NP cells. In addition, the luciferase reporter assay revealed that fibroblast growth factor 14 (FGF14) is a direct target of miR-154 and that the overexpression of FGF14 leads to similar effects as inhibition of miR-154 did. In conclusion, the results suggested that miR-154 participates in the development of IDD and its effects are mediated via targeting FGF14. Thus, miR-154 may be thought as a potential etiological factor for IDD and may provide insights into a therapeutic target to treat IDD.