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

Abstract

Context: Morphine is an alkaloid isolated from the poppy plants. The addiction of morphine is a very serious social issue. Some long non-coding RNAs (lncRNAs) have been proposed to engage in drug addiction. Objective: Whether lncRNA maternally expressed gene 3 (MEG3) attended to morphine-mediated autophagy of mouse hippocampal neuronal HT22 cells was probed. Materials and methods: HT22 cells were subjected to 10 µM morphine for 24 h. Cell autophagy was assessed by measuring LC3-II/LC3-I and Beclin-1 expression. qRT-PCR was carried out to measure MEG3 expression. SiRNA oligoribonucleotides targeting MEG3 (si-MEG3) was transfected to silence MEG3. The orexin1 receptor (OX1R), c-fos, p/t-ERK and p/t-PKC expressions were tested by western blotting. SCH772984 was used as an inhibitor of ERK pathway. Results: Morphine elevated OX1R (2.92 times), c-fos (2.06 times), p/t-ERK (2.04 times) and p/t-PKC (2.4 times), Beclin-1 (3.2 times) and LC3-II/LC3-I (3.96 times) expression in HT22 cells. Moreover, followed by morphine exposure, the MEG3 expression was also elevated in HT22 cells (3.03 times). The silence of MEG3 lowered the Beclin-1 (1.85 times), LC3-II/LC3-I (2.12 times), c-fos (1.39 times) and p/t-ERK (1.44 times) expressions in morphine-treated HT22 cells. Inhibitor of ERK pathway SCH772984 further promoted the influence of MEG3 silence on morphine-caused Beclin-1 (1.97 times) and LC3-II/LC3-I (1.92 times) expressions decreases. Conclusions: Up-regulation of MEG3 attended to the morphine-caused autophagy of HT22 cells might be through elevating c-fos expression and promoting ERK pathway activation. More experiments are also needed in the future to analyse the influence of other lncRNAs in drug addiction.

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

“…There have been many reports on the functions of lncRNA-Meg3, PDGFRA and miR-421 in tumours, suggesting that these three molecules have very important regulatory effects on tumour proliferation and invasion (35,37,(45)(46)(47)(48)(49)(50)(51)(52). However, there have been no reports discussing the three in combination.…”

Progress in understanding the role of lncRNA in programmed cell death

“…In addition, compared with the morphine + si-MEG3 group, Beclin-1 and LC3-II/LC3-I expression in HT22 cells in the morphine + si-MEG3 + SCH772984 group were further reduced. These experiments indicate that MEG3 upregulation may be involved in the effect of morphine on autophagy in HT22 cells by promoting ERK pathway activation 62 .…”

Transcriptomic Analysis of Long Non-coding RNA-MicroRNA-mRNA Interactions in the Nucleus Accumbens Related to Morphine Addiction in Mice

“…Although these lncRNAs have not been reported to be involved in drug addiction, dysregulated expression of lncRNAs has been reported to play a critical role in the progression of addiction ( 26 , 27 ). Gao et al showed that upregulation of MEG3 was involved in morphine-induced autophagy in hippocampal neuronal HT22 cells ( 28 ). In addition, analysis of significantly dysregulated miRNAs revealed many downregulated miRNAs, including miR-124 and miR-218, and upregulated miRNAs, including miR-451a and miR-15b-3p, were involved in drug addiction.…”