Abstract
MicroRNAs (miRNAs) are small endogenous non‐coding RNAs that can negatively regulate the expression of their complementary mRNA targets, and have been implicated in various pathophysiological processes. In this study, we examined the effect of miR‐222‐3p on intervertebral disc degeneration (IDD). We found that expression of miR‐222‐3p was significantly higher in IDD tissues than in normal intervertebral disc tissue, and report that overexpression of miR‐222‐3p remarkably increased apoptosis and reduced proliferation of nucleus pulposus (NP) cells. In addition, miR‐222‐3p promoted secretion of matrix metalloproteinase‐3, and decreased collagen type II and aggrecan production. Cyclin‐dependent kinase inhibitor 1B (CDKN1B) was identified as a direct target of negative regulation by miR‐222‐3p in NP cells, and expression of miR‐222‐3p was found to be negatively correlated with that of CDKN1B in IDD tissue. Finally, we observed that transfection with miR‐222‐3p dramatically reduced CDKN1B expression in NP cells. In conclusion, miR‐222‐3p may be involved in IDD development, possibly through targeting CDKN1B.
Highlights
MicroRNAs are small endogenous non-coding RNAs that can negatively regulate the expression of their complementary mRNA targets, and have been implicated in various pathophysiological processes
In the clinical tissues, using the quantitative real-time PCR (qRT-PCR) method, we found that the expression of miR-222-3p was greatly higher in intervertebral disc degeneration (IDD) tissues than in normal intervertebral disc tissues as well (Fig. 1B, P < 0.01)
In this study, when the miR-222-3p mimics and inhibitors were transfected into nucleus pulposus (NP) cells, we observed that the mRNA and protein level of collagen type II (COL2A1) and ACAN were decreased with miR-222-3p overexpression, while the mRNA and protein expression of matrix metalloproteinase-3 (MMP-3) was increased with overexpression of miR-222-3p (Fig. 3A–C)
Summary
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that can negatively regulate the expression of their complementary mRNA targets, and have been implicated in various pathophysiological processes. We found that expression of miR-222-3p was significantly higher in IDD tissues than in normal intervertebral disc tissue, and report that overexpression of miR-222-3p remarkably increased apoptosis and reduced proliferation of nucleus pulposus (NP) cells. Cyclin-dependent kinase inhibitor 1B (CDKN1B) was identified as a direct target of negative regulation by miR222-3p in NP cells, and expression of miR-222-3p was found to be negatively correlated with that of CDKN1B in IDD tissue. Growing evidence has confirmed that gradual degeneration of the nucleus pulposus (NP) is responsible for the development of IDD, and the imbalance of extracellular matrix (ECM). Abbreviations 30-UTR, 30-untranslated region; ACAN, aggrecan; CCK-8, cell counting kit-8; CDKN1B, cyclin-dependent kinase inhibitor 1B; COL2A1, collagen type II; ECM, extracellular matrix; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GEO, gene expression omnibus; IDD, intervertebral disc degeneration; miRNA, microRNA; MMP-3, matrix metalloproteinase-3; MT, mutant; NP, nucleus pulposus; qRT-PCR, quantitative realtime PCR. Finding specific targets on NP cells would help to better understand the development of IDD
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