LncRNA SNHG1 Delayed Fracture Healing via Modulating miR-181a-5p/PTEN Axis

Abstract

Background:The purpose of this study was to investigate the role of Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in delayed healing of tibial fractures and its potential regulatory mechanisms. Methods: 51 patients with normal healing of tibial fractures and 46 patients with delayed healing of tibial fractures were enrolled. RT-qPCR was performed to analyze SNHG1, microRNA (miRNA)-181a-5p, and PTEN levels. ROC curves were used to detect the predictive value of SNHG1 for delayed healing in fracture patients. Subsequently, the regulation of osteogenic markers by SNHG1 and miR-181a-5p was analyzed in MC3T3-E1. Cell proliferation and apoptosis were quantified by CCK-8 and flow cytometry. The binding between SNHG1/miR-181a-5p/PTEN was detected by dual-luciferase reporter gene assay. Results: Serum SNHG1 and PTEN expression were upregulated and miR-181a-5p expression was downregulated in patients with delayed fracture healing. SNHG1 decreased the level of osteogenic markers in MC3T3-E1, inhibited the proliferation, and stimulated apoptosis of MC3T3-E1 (P < 0.05). SNHG1 acted as a sponge for miR-181a-5p, and elevation of miR-181a-5p abolished the inhibition of osteogenic differentiation and promotion of apoptosis by SNHG1 (P < 0.05). PTEN was identified as a target of miR-181a-5p and involved in this regulatory process. Finally, elevated SNHG1 was a feasible predictive biomarker in patients with delayed fracture healing. Conclusion: The current study revealed that SNHG1/miR-181a-5p/PTEN axis inhibited osteoblast differentiation and proliferation and promoted apoptosis, thus leading to the inhibition of tibial fracture healing. Our findings contribute to the understanding of the mechanisms underlying delayed tibial fracture healing.

Keywords

• delayed fracture healing
• sngh1
• mir-181a-5p
• pten