Long non-coding RNA Snhg15 promotes preosteoblast proliferation by interacting with and stabilizing nucleolin

• Published in: Biochimica et biophysica acta. Molecular cell research 2024-12, Vol.1871 (8), p.119847, Article 119847
• Main Authors: Zhu, Jiaqi, Mo, Lijuan, Li, Mengying, Wang, Yunlei, Zhang, Gengming, Tao, Zhendong, Liao, Xiaozhu, Du, Mingyuan, He, Hong
• Format: Article
• Language: English
• Subjects: Cell cycle; lncRNA Snhg15; Nucleolin; Preosteoblasts; Proliferation
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119847

The proliferation and mineralization of preosteoblasts is crucial for bone formation and has attracted extensive attentions for decades. However, the roles of numerous long non-coding RNAs (lncRNAs) in preosteoblasts have not been fully determined. This study aimed to investigate the function of lncRNA Snhg15 in preosteoblasts as well as the potential underlying mechanism. LncRNA Snhg15 was dynamically expressed during preosteoblast proliferation and mineralization, and its transcripts were localized mainly in the cytoplasm. LncRNA Snhg15 knockdown significantly inhibited the proliferation and mineralization of preosteoblasts in both a cellular model and a murine ectopic bone formation model. RNA-seq showed that lncRNA Snhg15 knockdown downregulated multiple proliferation-related genes, and cell cycle deregulation was verified by flow cytometry. Mechanistically, we found that lncRNA Snhg15 could bind to nucleolin (NCL), thereby block NCL ubiquitination and decrease its degradation. Furthermore, the overexpression of NCL in lncRNA Snhg15-knockdown preosteoblasts ameliorated GO/G1 phase cell cycle arrest. Moreover, experiments in an in situ bone formation model confirmed the negative effects of lncRNA Snhg15 deficiency on bone formation. In conclusion, this study revealed an important regulatory role of lncRNA Snhg15/NCL complex in preosteoblast proliferation and may provide insights into the molecular mechanisms underlying bone formation. •LncRNA Snhg15 transcripts mainly located in the cytoplasm of preosteoblasts.•LncRNA Snhg15 promotes the proliferation and mineralization of preosteoblasts.•LncRNA Snhg15 promotes preosteoblast proliferation via regulating cell cycle progression.•The effects of lncRNA Snhg15 on cell cycle in preosteoblasts rely on interacting with nucleolin to maintain its stability.