ACSL4 suppresses glioma cells proliferation via activating ferroptosis

作者：Jing Cheng, Yanqin Fan, Bao‐Hui Liu, Han Zhou, Junmin Wang, Qianxue Chen · 发表于：Oncology Reports · 年份：2019 · DOI：10.3892/or.2019.7419 · 被引用次数：189 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Lipids, and Metabolism、Drug Transport and Resistance Mechanisms

Acyl‑CoA synthetase long‑chain family member 4 (ACSL4) is a member of the long chain family of acyl‑CoA synthetase proteins, which have recently been shown to serve an important role in ferroptosis. Previous studies have suggested that ferroptosis is involved in the occurrence of glioma; however, the role of ACSL4 in glioma remains unknown. In the present study, a reduction of ferroptosis in human glioma tissues and glioma cells was observed. Subsequently, it was demonstrated that the expression of ACSL4 was also downregulated in human glioma tissues and cells. A ferroptosis inhibitor and inducer were used to investigate the effects of ferroptosis on viability. The results showed that promoting ferroptosis inhibited the proliferation of glioma cells, and that the use of inducers had the reverse effect. Therefore, it was hypothesized that the reduction in ACSL4 expression may have been involved in ferroptosis and proliferation in glioma. Overexpression of ACSL4 decreased expression of glutathione peroxidase 4 and increased the levels of ferroptotic markers, including 5‑hydroxyeicosatetraenoic (HETE), 12‑HETE and 15‑HETE. Additionally, ACSL4 overexpression resulted in an increase in lactate dehydrogenase release and a reduction in cell viability. The opposite results were observed when ACSL4 was silenced. These findings suggest that ACSL4 regulates ferroptosis and proliferation of glioma cells. To further investigate the mechanism underlying ACSL4‑mediated regulation of prolife...