Overexpression of TUG1 promotes neuronal death after cerebral infarction by regulating microRNA-9.

OBJECTIVE

This study aims at investigating whether TUG1 (Taurine Upregulated Gene 1) can regulate FOXO3 expression through competitive binding to microRNA-9, thus leading to increased neuronal death and promoting the occurrence and development of acute cerebral infarction.

MATERIALS AND METHODS

TUG1 and FOXO3 expressions in cerebral cortical neurons of MCAO mice, control mice and primary neurons were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The effects of TUG1 and FOXO3 on neuronal apoptosis were determined by TUNEL after cerebral infarction area was stained with TTC. The binding condition of microRNA-9, TUG1 and FOXO3 was verified by the Luciferase reporter gene assay. Western blot was performed to detect the protein expressions of B-cell lymphoma-2 (BCL-2) and BCL2-Associated X (BAX) after altering the TUG1 or FOXO3 expression in primary neurons.

RESULTS

TUG1 and FOXO3 were overexpressed in cerebral cortical neurons of MCAO mice and primary neurons. The inhibition of TUG1 or FOXO3 resulted in less neuronal apoptosis. Luciferase reporter gene assay demonstrated that TUG1 regulates FOXO3 via TUG1/microRNA-9/FOXO3 regulatory network. Besides, TUG1 inhibited BCL-2 but promoted BAX expression in primary neurons.

CONCLUSIONS

The overexpression of TUG1 can promote neuronal death after cerebral infarction in mice by competitive binding to microRNA-9 and promotion of FOXO3 expression.