MiR-27a Regulates Apoptosis in Nucleus Pulposus Cells by Targeting PI3K
Open Access
- 25 September 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (9), e75251
- https://doi.org/10.1371/journal.pone.0075251
Abstract
The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3’-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.Keywords
This publication has 32 references indexed in Scilit:
- MicroRNAs and immunity: Novel players in the regulation of normal immune function and inflammationSeminars in Cancer Biology, 2008
- Expression of the Trp2 Allele of COL9A2 Is Associated With Alterations in the Mechanical Properties of Human Intervertebral DiscsSpine, 2007
- Hydrostatic Pressure Differentially Regulates Outer and Inner Annulus Fibrosus Cell Matrix Production in 3D ScaffoldsAnnals of Biomedical Engineering, 2007
- Biologic Response of the Intervertebral Disc to Static and Dynamic Compression In VitroSpine, 2007
- Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosisApoptosis, 2007
- miRNAs and apoptosis: RNAs to die forOncogene, 2006
- Stimulation of Gene Expression and Loss of Anular Architecture Caused by Experimental Disc Degeneration–An In Vivo Animal StudySpine, 2005
- Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ß gene polymorphismsEuropean Spine Journal, 2005
- Mechanical Conditions That Accelerate Intervertebral Disc Degeneration: Overload Versus ImmobilizationSpine, 2004
- Epidemiological features of chronic low-back painThe Lancet, 1999