circ_0003170 aggravates human hippocampal neuron injuries by regulating the miR-421/CCL2 axis in cells models of epilepsy.

Emerging evidence proposes that circular RNAs (circRNAs) are involved in epileptogenesis. This study aimed to investigate the role and the function mechanism of circ_0003170 in epilepsy models in vitro. Epilepsy models were established in human hippocampal neurons treated by magnesium-free (Mg2+-free) solution. The expression of circ_003170, miR-421 and C-C motif chemokine ligand 2 (CCL2) was detected by qRT-PCR. The putative interaction between miR-421 and circ_003170 or CCL2 was validated by dual-luciferase reporter assay and RIP assay. The protein level of CCL2 was detected by Western blot. Cell viability was detected by CCK-8 assay, and cell cycle and apoptosis were monitored by flow cytometry. The content of superoxide dismutase (SOD) and malondialdehyde (MDA) and the activity of caspase-3 were assessed using commercial kits. The results showed that circ_0003170 and CCL2 expression was enhanced, while miR-421 expression was declined in temporal lobe epilepsy serum specimens and Mg2+-free-induced neurons. circ_0003170 knockdown ameliorated Mg2+-free-induced cell cycle arrest, oxidative stress and apoptosis in neurons by enriching miR-421. Further analysis presented that miR-421 overexpression alleviated Mg2+-freeinduced cell injuries by depleting CCL2. CCL2 overexpression reversed the effects of circ_0003170 knockdown. Overall, circ_0003170 knockdown ameliorated Mg2+-free-induced human hippocampal neuron injuries by mediating the miR-421/CCL2 axis.

Citation

Fang Chen, Hongjia Zheng, Wenyu Zhang, Jie Kang, Qiao Liu, Juan Pu, Ling Yang. circ_0003170 aggravates human hippocampal neuron injuries by regulating the miR-421/CCL2 axis in cells models of epilepsy. General physiology and biophysics. 2021 Mar;40(2):115-126

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PMID: 33880998

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