MicroRNA-582-5p Reduces Propofol-induced Apoptosis in Developing Neurons by Targeting ROCK1

Abstract

Background: Propofol is an intravenous drug commonly used in anesthesia procedures and intensive care in children. However, it also has neurotoxic effects on children. MicroRNA plays an important role in neurological diseases and neurotoxicity. Methods: In this study, primary rat hippocampal neurons was used to investigate the role of miR-582-5p in propofol-induced neurotoxicity. Cell viability was monitored by 3-(4,5Dimethylthiazol- yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay, while the expression of proteins was monitored by real-time quantitation polymerase chain reaction (RT-qPCR) andwestern blot. TargetScan and double luciferase report assay were used to predict the targeting relationship between miR-582-5p and Rho-associated serine-threonine protein kinase 1 (ROCK1). Results: In the present study, the viability of neurons and the expression of miR-582-5p were decreased in a time-dependent manner after propofol treatment. Besides, miR-582-5p overexpression significantly reduced the toxicity of propofol on neuron cells, but had no significant effect on normal nerve cells. In addition, miR-582-5p overexpression significantly reversed the expression apoptosis-related proteins (cleaved caspase 3 and cleaved caspase 9) induced by propofol, but had no significant effect in normal nerve cells. TargetScan and Dual-luciferase report assay revealed that ROCK1 was a targeted regulatory gene for miR-582-5p, and propofol treatment up-regulated ROCK1 expression by inhibiting miR-582-5p expression. Notably, miR-582-5p overexpression significantly increased cell viability, while ROCK1 overexpression reversed the effect of miR-582-5p. Conclusion: Taken together, these findings suggest that miR-582-5p alleviated propofol-induced apoptosis of newborn rat neurons by inhibiting ROCK1.

RETRACTED ARTICLE: Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals

“…Specifically, the following findings from cell culture models showed that miR-15a-5p [53], MicroRNA-582-5p [54] and miR-34a [55] were involved in propofol-induced neuron and astrocyte death, respectively; miR-21 was involved in propofol-induced inhibition of proliferation and epithelial-mesenchymal transition in breast cancer cells [56]; miR-495 was involved in propofol-induced inhibition of proliferation and metastasis in JEG-3 choriocarcinoma cells [57]. In this study, propofol treatment decreased cell migration followed by miR-34a and E-cadherin upregulation in the PANC-1 cells.…”

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction

“…Jiang et al, 2019). Recently, an increasing number of microRNA molecules [miR-21 (Twaroski et al, 2014), miR-206 (Li et al, 2017), miR-34a (Li et al, 2018), miR-215 (Tang et al, 2020), miR-363-3p (Yao and Zhang, 2020), miR-455-3p (Zhu et al, 2020), miR-9-5p (Zhang et al, 2022), and miR-582-5p (Zhang et al, 2020b)] have been revealed to be associated with propofol-induced neuronal apoptosis.…”

“…Historically, miR-665 in anesthesia-induced neurotoxicity was believed to directly down-regulate anti-apoptotic gene Bcl-2l1 expression, increasing caspase-3-mediated apoptosis rates ( Sun and Pei, 2015 , 2016 ; Sun et al, 2015 ; Jiang et al, 2019 ). Recently, an increasing number of microRNA molecules [miR-21 ( Twaroski et al, 2014 ), miR-206 ( Li et al, 2017 ), miR-34a ( Li et al, 2018 ), miR-215 ( Tang et al, 2020 ), miR-363-3p ( Yao and Zhang, 2020 ), miR-455-3p ( Zhu et al, 2020 ), miR-9-5p ( Zhang et al, 2022 ), and miR-582-5p ( Zhang et al, 2020b )] have been revealed to be associated with propofol-induced neuronal apoptosis. Meanwhile, the relationship between several microRNA types [miR-124 ( Yang et al, 2019 ), miR-153 ( Shao et al, 2019 ), miR-106a ( Zhang et al, 2020a ), and miR-142-5p ( Xie et al, 2020 )] and isoflurane-induced neuronal apoptosis has been demonstrated.…”

Anaesthesia and brain development: a review of propofol-induced neurotoxicity in pediatric populations

“…8,9 At present, in vivo and in vitro experiments have shown that propofol is neurotoxic to the developing brain, can cause damage to developing nerve cells, and can interfere with the learning and memory function of animals. [10][11][12] In case reports and clinical studies, it was found that children under propofol anesthesia experience neuromuscular damage, resulting in various changes, such as tendon hyperreflexia, muscle weakness, visual memory impairment, and cognitive impairment. 13 Due to the neurotoxicity of propofol found in both laboratory and clinical studies, the safety of propofol anesthesia in pregnant women and children has received widespread attention.…”