Downregulation of HOTAIR reduces neuronal pyroptosis by targeting miR-455-3p/NLRP1 axis in propofol-treated neurons in vitro.

In this study, propofol treatment significantly reduced neuronal the viability of neurons, and promoted the expression of inflammation-related factors. Propofol treatment also promoted neuron death and neuronal pyroptosis. All the above effects might be related to the propofol-induced overexpression of HOTAIR. Interestingly, knockdown of HOTAIR by shRNA (sh-HOTAIR) significantly inhibited neuronal pyroptosis, but increased neuronal viability. Further analysis showed that HOTAIR and Nod-like receptor protein1 (NLRP1) were the targets of miR-455-3p, respectively. Notably, propofol treatment decreased the level of miR-455-3p, while increased the level of NLRP1. In addition, sh-HOTAIR increased the level of miR-455-3p, which further inhibited the expression of NLRP1 and the activation of NLRP1 inflammasome, thereby inhibiting neuronal pyroptosis. More importantly, NLRP1 overexpression decreased neuronal viability, and reactivated NLRP1 inflammasome, thus reversing the inhibitory effect of sh-HOTAIR on pyroptosis. Our findings indicated that HOTAIR inhibited propofol-induced pyroptosis of neurons by regulating miR-455-3p/NLRP1 axis, indicating that HOTAIR may be a potential therapeutic target for propofol-induced neurotoxicity. PMID: 33534059 [PubMed - as supplied by publisher]
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research