Hsa-circ-0007292 promotes the osteogenic differentiation of posterior longitudinal ligament cells via regulating SATB2 by sponging miR-508-3p

Hsa-circ-0007292 通过海绵作用 miR-508-3p 调控 SATB2 促进后纵韧带细胞成骨分化

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作者:Anlong Jiang, Nanxiang Wang, Xinxing Yan, Yunheng Jiang, Chengchao Song, Hui Chi, Guanghua Chen, Feng Wu, Ye Ji, Jinglong Yan

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is a disorder with multiple pathogenic mechanisms and leads to different degrees of neurological symptoms. Recent studies have revealed that non-coding RNA (ncRNA), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), could influence the development of OPLL. Nevertheless, the molecular mechanisms linking circular RNAs (circRNAs) and the progression of OPLL is still unknown. The current research explored the expression profiles of OPLL-related circRNAs by microarray analysis, and applied qRT-PCR to validate the results. Subsequently, we confirmed the upregulation of hsa_circ_0007292 in OPLL cells by qRT-PCR and validated the circular characteristic of hsa_circ_0007292 by Sanger sequencing. Fluorescence in situ hybridization (FISH) unveiled that hsa_circ_0007292 was predominantly located in the cytoplasm. Functionally, gain-of-function and loss-of-function experiments showed that hsa_circ_0007292 promoted the osteogenic differentiation of OPLL cells. Mechanistically, the interaction of hsa_circ_0007292 and miR-508-3p was predicted and validated by bioinformatics analysis, dual-luciferase reporter assays, and Ago2 RNA immunoprecipitation (RIP). Similarly, we validated the correlation between miR-508-3p and SATB2. Furthermore, rescue experiments were performed to prove that hsa_circ_0007292 acted as a sponge for miR-508-3p, and SATB2 was revealed to be the target gene of miR-508-3p. In conclusion, our research shows that hsa_circ_0007292 regulates OPLL progression by the miR-508-3p/SATB2 pathway. Our results indicate that hsa_circ_0007292 can be used as a promising therapeutic target for patients with OPLL.

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