1. A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes.
- Author
-
Nakajima, Masahiro, Koido, Masaru, Guo, Long, Terao, Chikashi, and Ikegawa, Shiro
- Subjects
- *
LONGITUDINAL ligaments , *NON-coding RNA , *OSSIFICATION , *GENE expression , *SPINE , *GENOME-wide association studies - Abstract
Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common intractable disease that causes spinal stenosis and myelopathy. We have previously conducted genome-wide association studies for OPLL and identified 14 significant loci, but their biological implications remain mostly unclear. Here, we examined the 12p11.22 locus and identified a variant in the 5′ UTR of a novel isoform of CCDC91 that was associated with OPLL. Using machine learning prediction models, we determined that higher expression of the novel CCDC91 isoform was associated with the G allele of rs35098487. The risk allele of rs35098487 showed higher affinity in the binding of nuclear proteins and transcription activity. Knockdown and overexpression of the CCDC91 isoform in mesenchymal stem cells and MG-63 cells showed paralleled expression of osteogenic genes, including RUNX2 , the master transcription factor of osteogenic differentiation. The CCDC91 isoform directly interacted with MIR890 , which bound to RUNX2 and decreased RUNX2 expression. Our findings suggest that the CCDC91 isoform acts as a competitive endogenous RNA by sponging MIR890 to increase RUNX2 expression. Nakajima et al. identified a functional variant in the 5′ UTR of a novel non-coding isoform of CCDC91 within the known 12p11.22 genome-wide association study locus for ossification of the posterior longitudinal ligament of the spine. The isoform directly interacts with MIR890 , which binds to RUNX2 and regulates osteogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF