Silencing MEG3 protects PC12 cells from hypoxic injury by targeting miR-21

Abstract

Increasing number of literatures highlighted lncRNA maternally expressed gene 3 (MEG3) as an emerging target for hypoxic-ischaemic brain damage (HIBD). This study attempted to assess the role of MEG3 in a cell model of HIBD. Expression of MEG3 in PC12 cells was suppressed by siRNA-mediated transfection, after which the cells were subjected to hypoxia. Cell viability, apoptosis, migration and the expression of related proteins were assessed. Furthermore, the downstream gene of MEG3 and its downstream signalling pathways were explored. We found that, down-regulation of MEG3 prevented hypoxic injury in PC12 cells, as hypoxia induced viability loss, apoptosis and migration repression were attenuated by transfection with MEG3 siRNA. Meanwhile, MEG3 acted as a miR-21 sponge. The neuroprotective functions of MEG3 silence were flattened when miR-21 was suppressed. Moreover, the deactivation of PI3K/AKT pathway and the activation of NF-jB pathway induced by hypoxia were attenuated by MEG3 silence. As expected, the effects of MEG3 silence on these two signalling were via miR-21. In conclusion, the neuroprotective effects of MEG3 silence on PC12 cells injured by hypoxia were observed in this study. Mechanistically, the neuroprotective effects of MEG3 silence on PC12 cells were via sponging miR-21 and thus regulating PI3K/AKT and NF-jB pathways. HIGHLIGHTS 1. MEG3 is highly expressed in PC12 cells following hypoxic injury; 2. Silence of MEG3 prevents hypoxia-induced cell damage in PC12 cells; 3. MEG3 acts as a miR-21 sponge; 4. MEG3 sponges miR-21 to regulate PI3K/AKT and NF-jB pathways.

MEG3-Mediated Oral Squamous Cell Carcinoma-Derived Exosomal miR-421 Activates Angiogenesis by Targeting HS2ST1 in Vascular Endothelial Cells

“…In terms of the role of ceRNA, lncRNA MEG3 can bind different miRNAs like a "sponge" and contribute to the regulatory network of miRNAs. For example, the neuroprotective effect of MEG3 silencing on PC12 cells is through the regulation of PI3K/AKT and NF-kB pathways by sponging miR-21 [44]. Likewise, another study showed that down-expression of MEG3 could promote the proliferation of colonic stem cells in early colorectal cancer through binding miR-708 [45].…”

Long non-coding RNA MEG3 promotes tumor necrosis factor-alpha induced oxidative stress and apoptosis in interstitial cells of cajal via targeting the microRNA-21 /I-kappa-B-kinase beta axis

“…It is of great significance for the management of related diseases to investigate the mechanism of ICC loss. Recently, MEG3 is reported to promote inflammation, apoptosis, and oxidative stress in various cells, while its known target miR-21 plays the opposite role [ 22 , 43–45 ]. However, their functions in ICC have not been revealed yet.…”

“…Recent studies suggest that miR-21 can protect cell from oxidative stress and apoptosis [ 19–21 ]. Interestingly, increasing evidences show that miR-21 is negatively regulated by MEG3 in different types of tissues [ 22–24 ]. The interaction between MEG3 and miR-21 and their function in ICC have not been studied yet.…”

LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State

“…To further emphasize the biological functions of MEG3, they also silenced the lcnRNA in a focal cerebral ischemia and reperfusion model induced by intraluminal MCAO. Indeed, they found that silencing MEG3 leads to protection against in vivo I/R-induced ischemic damage and improved overall neurological functions [95,96].…”