LncRNA TSIX aggravates spinal cord injury by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis.

Long noncoding RNA (lncRNA)-X-inactive-specific transcript (TSIX) expression is upregulated in spinal cord tissues following spinal cord injury (SCI). However, the role of lncRNA-TSIX in SCI remains elusive. SCI animal model was established using C57BL/6 mice. LncRNA TSIX and miR-532-3p expression were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Apoptosis, cell proliferation, and migration were evaluated by transferase dUTP nick end labeling staining, CCK-8, and Transwell assays, respectively. The interaction of miR-532-3p with lncRNA TSIX and DDOST was explored via a dual-luciferase reporter system. Hematoxylin-eosin staining and the Basso, Beattie, and Bresnahan locomotor rating (BBB) scale were performed to investigate SCI progression. The expression of the lncRNA TSIX was found to be significantly upregulated in the serum of SCI patients and spinal cord tissues of SCI mice. The overexpression of lncRNA TSIX enhanced spinal cord neural stem cell (SC-NSC) proliferation and migration in vitro while inhibiting apoptosis and inflammatory cell infiltration in vivo. Moreover, lncRNA TSIX acted as a molecular sponge for miR-532-3p, and the knockdown of miR-532-3p promoted proliferation and migration and inhibited apoptosis of SC-NSCs. Moreover, DDOST was found to be the downstream target of miR-532-3p, and DDOST overexpression showed a similar effect as miR-532-3p silencing on the proliferation, migration, and apoptosis of SC-NSCs. Furthermore, we found that lncRNA TSIX overexpression promoted the activation of the PI3K/AKT signaling pathway. LncRNA TSIX aggravates SCI by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis, indicating potential applications for targeted therapy of SCI regeneration.