Abstract
Excessive oxidative stress causes neuronal cell injury. Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) is a MYC-interacting LncRNA. Its expression and potential functions in hydrogen peroxide (H2O2)-stimulated neuronal cells are studied. In SH-SY5Y neuronal cells and primary human neuron cultures, H2O2 downregulated Lnc-EPIC1 and key MYC targets (Cyclin A1, CDC20 and CDC45). Ectopic overexpression of Lnc-EPIC1 increased expression of MYC targets and significantly attenuated H2O2-induced neuronal cell death and apoptosis. Contrarily, Lnc-EPIC1 siRNA potentiated neuronal cell death by H2O2. MYC knockout by CRISPR/Cas9 method also facilitated H2O2-induced SH-SY5Y cell death. Significantly, MYC knockout abolished Lnc-EPIC1-induced actions in H2O2-stimulated neuronal cells. Together, these results suggest that Lnc-EPIC1 downregulation mediates H2O2-induced neuronal cell death.
Highlights
Neurons in the central nerve system (CNS) are vulnerable to reactive oxygen species (ROS) overproduction and excessive oxidative injury
In order to study the potential effect of Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) in neuronal cells, differentiated SH-SY5Y neuronal cells were treated with hydrogen peroxide (H2O2)
LncRNAs are important for genomic imprinting, cell cycle progression, cell survival, differentiation and development [11, 12, 23]
Summary
Neurons in the central nerve system (CNS) are vulnerable to reactive oxygen species (ROS) overproduction and excessive oxidative injury. It is possibly due to the high rate of oxygen consumption, enrichment of polyunsaturated fatty acids and defective Nrf cascade in neurons [1,2,3,4,5]. Excessive oxidative stress will induce profound neuronal cell injury, serving as a key pathogenesis mechanism of neurodegenerative diseases [1,2,3,4]. H2O2 overproduction can induce profound lipid peroxidation, DNA breaks, protein damage and eventually neuronal cell death and apoptosis [7, 9, 10]. Understanding the molecular mechanisms of H2O2induced neuronal cell death is vital for developing possible intervention strategies
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