Long non-coding RNAs plasmacytoma variant translocation 1 regulates bone marrow mesenchymal stem cell transplantation to promote the repair of spinal cord injury.

Abstract

This study investigated the therapeutic potential of long non-coding RNAs plasmacytoma variant translocation 1 (lncRNA PVT1) in regulating the function of bone marrow mesenchymal stem cells (BMSCs) following experimental spinal cord injury (SCI). Rat BMSCs were isolated and characterized. Loss-of and gain-of-function experiments were performed to assess the effects of lncRNA PVT1 on BMSCs and Schwann cells (SCs). Fusion PCR mutation, dual-luciferase reporter, and RNA immunoprecipitation assays were employed to explore the binding region between lncRNA PVT1 and polypyrimidine tract binding protein 1 (PTBP1). LncRNA PVT1 increased the proliferation, migration, and apoptosis of BMSCs; lncRNA PVT1 knockdown had the opposite effects. LncRNA PVT1 inhibited PTBP1 expression. The promoting effect of lncRNA PVT1 on the proliferation and migration of BMSCs was suppressed by overexpression of PTBP1. LncRNA PVT1 also induced SC-like differentiation of BMSCs. LncRNA PVT1-modified BMSCs promoted the proliferation and migration of SCs and upregulated levels of neurotrophic factors and SC biomarkers. Transplantation of lncRNA PVT1-modified BMSCs also improved functional recovery of rats with SCI. Altogether, lncRNA PVT1 promoted the proliferation, migration, and differentiation of BMSCs by inhibiting PTBP1. LncRNA PVT1-modified BMSCs also influenced the function of SCs and promoted recovery in rats following SCI.