Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway

Gao, Shuibo; Li, Enyao; Gao, Haixia

Morphine is one of the most abundant alkaloids isolated from the poppy plants (Du 2018) . Although morphine has strong analgesic activity, the addiction of morphine also is a very serious social issue (Kim et al. 2016; Antolak et al. 2017 ). Many efforts have been made to explore the molecular basis of morphine addiction and some molecules and cellular biological processes have been found. OX1R, c-fos, ERK and PKC pathways are all discovered to join in morphine addiction. For example, Erami et al. (2012) reported that suppression of OX1R decreased the progress of morphine tolerance and physical dependence in rats. Siahposht-Khachaki et al. (2018) indicated that exposure to morphine produced an elevation of c-fos expression in nucleus accumbens, prefrontal cortex and hippocampus of Wistar rats. In addition, Liu et al. (2016) illustrated that ERK pathway contributed to the maintenance of morphine-mediated memory in hippocampus. Pena et al. (2018) pointed out that followed by morphine stimulation, PKC pathway in mouse neuroblastoma cells was activated. As an intracellular protein self-degradation Figure 2 . Morphine promoted HT22 cell autophagy. HT22 cells were exposed to 10 mM morphine for 24 h. The Beclin-1 and LC3 protein levels were tested by western blotting. ÃÃ p ˂ 0.01. process capable of upholding cellular metabolism, cell autophagy also has been demonstrated to take part in morphine-mediated drug addiction (Lixia et al. 2010; Su et al. 2017 ). In the cell autophagy process, the LC3-I binds to phosphatidylethanolamine to form LC3-II, which joins in the formation of autophagosome membranes (Pugsley 2017) . Beclin-1, also known as Atg6, is a key regulator of cell autophagy (Booth et al. 2014) . Herein, we found that the OX1R, c-fos, p/t-ERK and p/t-PKC expressions in HT22 cells were all increased after morphine stimulation. The LC3-II/LC3-I and Beclin-1 expressions were also elevated in HT22 cells after morphine stimulation. Therefore, we proposed that morphine-stimulated HT22 cells could be utilized as an in vitro cell model of morphine addiction to explore the influence of MEG3 on morphine addiction.