Circ_HECTD1 regulates cerebral ischemia injury via mechanisms involving the regulation of let-7c-5p/ROCK1 axis.

Qian Guo, Tingting Guo, Yuanyuan Sun, Tianrong Chen

Neuroreport 2022 Jan 05

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Ischemia is the main cause of cerebral ischemic stroke with a high mortality rate, and it is affected by the dysfunction of circular RNAs. The underlying molecular mechanisms of circ_HECTD1 were explored in cerebral ischemia stroke. PC-12 cells were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) as the cell model of cerebral ischemia model. The expression levels of circ_HECTD1, let-7c-5p, and Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) were determined by quantitative real-time PCR in PC-12 cells. The proliferation ability of PC-12 cells was assessed by 5-ethynyl-2'-deoxyuridine and 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide assays. The protein expression levels were quantified by western blot analysis. Flow cytometry was performed to analyze cell apoptosis. Lactate dehydrogenase concentration was assessed by a commercialized kit. Dual-luciferase reporter assay was used to confirm the interaction relationships among circ_HECTD1, let-7c-5p and ROCK1. Circ_HECTD1 was upregulated in OGD/R-treated PC-12 cells. The results also showed that cell proliferation was decreased and apoptosis was increased in OGD/R-treated PC-12 cells, which was overturned by the inhibition of circ_HECTD1. Let-7c-5p was a target of circ_HECTD1, and the protective effects of circ_HECTD1 knockdown on OGD/R-treated PC-12 cells were canceled after co-transfection with let-7c-5p inhibitor. We found that ROCK1 was a potential target of let-7c-5p. Let-7c-5p -mediated the effects on the proliferation and apoptosis of OGD/R-treated PC-12 cells by targeting ROCK1. Circ_HECTD1 was implicated in the development of cerebral ischemia stroke. Knockdown of circ_HECTD1 protected against cerebral ischemia injury in OGD/R-treated PC-12 cells depending on the regulation of let-7c-5p/ROCK1 axis. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Qian Guo, Tingting Guo, Yuanyuan Sun, Tianrong Chen. Circ_HECTD1 regulates cerebral ischemia injury via mechanisms involving the regulation of let-7c-5p/ROCK1 axis. Neuroreport. 2022 Jan 05;33(1):13-22