长链非编码RNA（lncRNA）在环境外源性化学物质对身体造成损害中发挥了至关重要的作用，然而较少的研究探讨了它们在苯和其代谢产物羟基苯（HQ）暴露期间的影响。一种新兴的lncRNA，LINC01480，被发现与某些癌症的免疫微环境有关，但其具体功能尚不清楚。因此，本研究旨在研究LINC01480在HQ诱导的细胞凋亡中的作用。通过功能增强和功能丧失实验来研究LINC01480的生物学功能。在机械上，进行了核-细胞质分离实验、染色质免疫共沉淀（ChIP）、双荧光素酶报告基因实验和救援实验。在本研究中，当TK6细胞经过12、24、48和72小时的HQ（0、5、10和20μM）处理后，LINC01480的表达呈剂量依赖性增加。同时，PI3K和AKT的磷酸化水平下降，细胞凋亡增加。与对照组相比，LINC01480沉默后，HQ诱导的细胞凋亡显著降低，TK6细胞的相对存活率增加，而LINC01480的过表达则进一步增加了TK6细胞对HQ诱导的细胞凋亡的敏感性。LINC01480在TK6细胞中负调节PI3K/AKT通路，LINC01480沉默后抑制细胞凋亡的效果在抑制PI3K/AKT通路后得到了逆转。此外，ChIP和双荧光素酶报告基因实验表明，转录因子Foxo3a通过直接结合LINC01480的启动子区域-149至-138促进LINC01480转录。此外，短时羟基苯曝露促进了Foxo3a的表达。从这些发现中，我们可以得出结论，LINC01480受Foxo3a激活，并通过抑制PI3K/AKT通路促进HQ引起的细胞凋亡，表明LINC01480可能成为治疗HQ引起的毒性的可能靶点。版权所有©2023 Elsevier Inc.出版。

Long non-coding RNAs (lncRNAs) have been shown to play a critical role in the damage caused to the body by environmental exogenous chemicals; however, few studies have explored their effects during exposure to benzene and its metabolite, hydroquinone (HQ). An emerging lncRNA, LINC01480, was found to be associated with the immune microenvironment of some cancers, but its specific function remains unknown. Therefore, this study aimed to investigate the role of LINC01480 in HQ-induced apoptosis. The biological function of LINC01480 was investigated through gain-of-function and loss-of-function experiments. Mechanically, nuclear-cytoplasmic fractionation experiment, chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, and rescue experiments were performed. In this study, when TK6 cells were treated with HQ (0, 5, 10, and 20 μM) for 12, 24, 48, and 72 h, the expression of LINC01480 was increased in a dose-dependent manner. Meanwhile, the phosphorylation levels of PI3K and AKT decreased, and apoptosis increased. As compared to the control group, HQ-induced apoptosis was significantly reduced, and the relative survival rate of TK6 cells increased after silencing LINC01480, while overexpression of LINC01480 further sensitized TK6 cells to HQ-induced apoptotic cell death. LINC01480 negatively regulated the PI3K/AKT pathway in TK6 cells, and the apoptosis-inhibiting effect of LINC01480 silencing was reversed after inhibition of the PI3K/AKT pathway. In addition, ChIP and the dual-luciferase reporter assays showed that the transcription factor Foxo3a promoted LINC01480 transcription by directly binding to the promoter regions - 149 to - 138 of LINC01480. Moreover, short-term HQ exposure promoted the expression of Foxo3a. From these findings, we can conclude that LINC01480 is activated by Foxo3a, and promotes HQ-induced apoptosis by inhibiting the PI3K/AKT pathway, suggesting that LINC01480 might become a possible target for therapeutic intervention of HQ-induced toxicity.Copyright © 2023. Published by Elsevier Inc.