Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14
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Accumulating evidence suggests that microRNAs (miRNAs) play an important role in intervertebral disc degeneration (IDD), but the precise role of specific miRNAs involved in this disease remains elusive. The purpose of this study was to identify IDD-specific miRNAs, followed by functional validation of results. MiRNA expression profile was determined in nucleus pulposus (NP) tissues from patients with IDD and controls, employing Solexa sequencing and quantitative real-time PCR (qRT-PCR). Biological functions of differential expression miRNAs were further investigated in vitro and in vivo. Luciferase reporter assays and Western blotting were performed to determine miRNA targets. We identified 28 miRNAs that were differentially expressed in patients compared with controls. Following qRT-PCR confirmation, miR-193a-3p was significantly down-regulated in degenerative NP tissues. Moreover, its level was correlated with grade of disc degeneration. Through gain- and loss-of-function studies, miR-193a-3p was demonstrated to significantly promote type II collagen expression in NP cells. Knockdown of MMP14 induced effects on NP cells similar to those induced by miR-193a-3p. Bioinformatics target prediction identified MMP14 as a putative target of miR-193a-3p. Furthermore, luciferase reporter assays and Western blotting demonstrated that miR-193a-3p directly targets MMP14. MiR-193a-3p inhibited IDD in vitro and in vivo. The downregulation of miR-193a-3p induces the expression of MMP14, which promotes loss of type II collagen and thereby contributes to the development of human IDD. Our findings extend the role of miR-193a-3p in the pathogenesis of IDD and provide a potential novel therapeutic target for degenerative disc disease.
Intervertebral disc degeneration (ICC)-specific miRNA profile generated by next generation sequencing.
Downregulation of miR-193a-3p promoted loss of type II collagen by directly targeting MMP14 in IDD.
miR-193a-3p inhibited IDD in vitro and in vivo.
miR-193a-3p may be a promising candidate for prevention of degenerative disc disease.
KeywordsmicroRNAs Intervertebral disc degeneration miR-193a-3p MMP14
We thank all donors enrolled in the present study.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Wang Chen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Wang C, Ji ML, and Zhang XJ were involved in study conception and design. Ji ML, Shi PL, Chen H, and Chang Q were responsible for acquisition of data. Ji ML, Lu J, and Wang SZ analyzed and interpreted the data. Ji ML prepared the manuscript.
Compliance with ethical standards
This work was supported by “The Fundamental Research Funds for the Central Universities (3290005422).
Conflict of interest
The authors declare no conflict of interest.
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