Dysregulated MiR-3150a-3p Promotes Lumbar Intervertebral Disc Degeneration by Targeting Aggrecan

Abstract

Background/Aims: Low back pain has become one of the most common musculoskeletal diseases in the world. Studies have shown that intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the mechanisms underlying IDD remain largely unknown. Research over the past decade has suggested critical roles for microRNAs (miRNAs) in natural growth and disease progression. However, it remains poorly understood whether circular RNAs participate in IDD. Methods: Clinical IDD samples were collected from 20 patients who underwent discectomy. Weighted gene co-expression network analysis was used to identify the co-expression miRNA network modules (highly co-expressed clusters of miRNAs) that were associated with IDD grade. Results: miR-3150a-3p was the most significantly up-regulated miRNA in module “Blue.” Notably, aggrecan (ACAN) was identified as a direct target gene of miR-3150a-3p and ACAN expression was regulated by miR-3150a-3p. Overexpression of miR-3150a-3p decreased ACAN expression in nucleus pulposus cells, whereas inhibition of miR-3150a-3p increased ACAN expression. In addition, ACAN expression was negatively correlated with IDD grade. Conclusion: Our study suggests that the reduction of ACAN expression induced by the upregulation of miR-3150a-3p might participate in the development of IDD.

Melatonin attenuates TNF‐α and IL‐1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis

“…These data suggest that melatonin reduces TNF‐α and IL‐1β production not only through the PI3K/AKT, ERK, and NF‐κB pathways, but also via upregulation of miR‐3150a‐3p expression. The inhibition of miR‐3150a‐3p expression has been indicated in breast cancer and, in a recent study, upregulation of miR‐3150a‐3p was found to promote lumbar intervertebral disk degeneration by targeting aggrecan …”

“…The inhibition of miR-3150a-3p expression has been indicated in breast cancer and, in a recent study, upregulation of miR-3150a-3p was found to promote lumbar intervertebral disk degeneration by targeting aggrecan. 54 Melatonin receptors consist of 7 transmembrane-spanning proteins and two major subtypes, MT1 and MT2, encoded by the MTNR1A and MTNR1B genes, respectively. 55 The localization of these two receptors differs physically, indicating that they play different roles and functions in various situations.…”

Systematic identification of lincRNA‐based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma

“…We identified coexpression modules based on expression of all lincRNAs and PCGs using WGCNA R software . WGCNA module detection was conducted using an unsigned type of topological overlap matrix (TOM), a power β of 10, a minimal module size of 20, and a branch merge cut height of 0.25 . A FDR value of <0.05 by the permutation test was considered significant.…”

“…[29][30][31][32] WGCNA module detection was conducted using an unsigned type of topological overlap matrix (TOM), a power β of 10, a minimal module size of 20, and a branch merge cut height of 0.25. 33 A FDR value of <0.05 by the permutation test was considered significant. The dysfunctional lincRNA modules were enriched with differentially expressed lincRNAs (at least 1 lincRNA/module) or PCGs (hypergeometric test, FDR < 0.05).…”

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

“…Our results found miR-4450 was significantly up-regulated in IDD, which highlights its possible role in the pathogenesis of IDD, and the inhibition of miR-4450 may help protect NP. Two other studies further confirmed this trend [25,26]. Therefore, the overexpression of miR-4450 in NP of IDD patients highlights its possible role in the pathogenesis of IDD, and the inhibition of miR-4450 may help protect NP.…”