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| Mechanism of iron death induced by hsa_circ_0006988 in glioma cells |
| ZHAO Shuiqiang MENG Dawei CHEN Guoqiang LI Liangliang WANG Zhiwen HU Tiantian NIU Jianxing |
Department of Neurosurgery, Beijing Aviation General Hospital, Beijing 100012, China
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Abstract Objective To investigate the mechanism of hsa_circ_0006988 (circ_0006988) induced iron death in glioma cells. Methods The expression level of circ_0006988 in normal glioma cells HEB, A172, SHG44, and CHG-5 in gliomacells were detected. Glioma cells CHG-5 were then divided into Control group (blank control), si-NC group (transfected with siRNA control), si-circ group (transfected with circ_0006988 siRNA), si-Nrf2 group (transfected with Nrf2 siRNA), si-circ+Vector group (co-transfected circ_0006988 siRNA and negative control vector), si-circ+Nrf2 group (co-transfected circ_0006988 siRNA and Nrf2 overexpression vector). The expression of circ_0006988 in each group was detected by qRT-PCR. The content of Fe2+ was detected by colorimetry, the protein expressions of Nrf2, GPX4, Ferritin, TF, and TFR were detected by Western blot, ROS was detected by DCFHDA, and MDA was detected by thiobarbituric acid. Results The expression level of circ_0006988 in glioma cells A172, SHG44, and CHG-5 were higher than those in normal glioma cells (P＜0.05). The expression level of circ_0006988 in glioma cells A172 and SHG44 were lower than those of CHG-5 (P＜0.05). The contents of Fe2+, ROS, and MDA in glioma cells of si-circ group were higher than those of Control and si-NC group, and the protein expressions of Ferritin, TF, and TFR were higher than those of Control group and si-NC group (P＜0.05), while the protein expressions of Nrf2 and GPX4 were lower than those of Control group and si-NC group (P＜0.05). The protein expressions of Nrf2 and GPX4 in glioma cells in si-circ group were lower than those in si-NC group, the content of Fe2+, the protein expressions of Ferritin, TF and TFR, and the contents of ROS and MDA in glioma cells in si-NC group were higher than those in si-NC group (P＜0.05). The expression of Nrf2 and GPX4 proteins in glioma cells in si-circ+Nrf2 group were higher than that in si-circ+Vector group, the content of Fe2+, Ferritin, TF， and TFR proteins, the ROS and MDA contents in si-circ+Vector group were lower than those in si-circ+Vector group (P＜0.05). Conclusion Down-regulation of circ_0006988 can induce ferroptosis of glioma cells by inhibiting Nrf2/GPX4 signal.
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