PVT1 regulates hippocampal neuron apoptosis and inflammation in epilepsy by miR-206-3p-dependent regulation of CAMK4.

Abstract

This study was designed to dissect the function of plasmacytoma variant translocation 1 (PVT1) in hippocampal neuron injury in epilepsy and its possible molecular basis. Status epilepticus (SE) mouse model was built and primary hippocampal neurons were isolated. qRT-PCR and Western blot were applied to quantify the levels of related genes and proteins. Cell proliferation and apoptosis were examined by CCK-8, EdU, and flow cytometry assays. Inflammatory factors were detected using ELISA analysis. Dual-luciferase reporter and RIP assays were carried out to validate the relationship between miR-206-3p and PVT1 or CAMK4. PVT1 and CAMK4 were increased, and miR-206-3p was downregulated in the hippocampus and hippocampal neurons of SE mice. Knockdown of PVT1 or CAMK4 abated SE-induced proliferation inhibition, apoptosis, and inflammation in hippocampal neurons. Mechanistically, PVT1 could sponge miR-206-3p to upregulate the expression of CAMK4 in hippocampal neurons. Moreover, downregulation of miR-206-3p reversed the inhibitory effects of PVT1 knockdown on SE-induced apoptosis and inflammation in hippocampal neurons. Similarly, overexpression of CAMK4 abolished miR-206-3p-evoked arrest of apoptosis and inflammation in hippocampal neurons under SE condition. Collectively, PVT1 contributed to SE-induced apoptosis and inflammation in hippocampal neurons by modulating the miR-206-3p/CAMK4 axis, offering a novel insight into the prevention of epilepsy.