Long-term exposure to benzene is associated with adverse health effects such as leukemia. Abnormal cell cycle progression has been reported participating in tumorigenesis. Our previous study found that lncRNA-OBFC2A was involved in benzene toxicity through regulating cell proliferation. However, the function of lncRNA-OBFC2A in the regulation of cell cycle remains obscure and the precise mechanisms need to be explored. In vitro study, results showed that benzene metabolic, 1,4-Benzoquinone (1,4-BQ), induced cell cycle arrest at the G1 phase accompanied with decreased expression of Cyclin D1 in a dose-dependently manner. Interestingly, lncRNA-OBFC2A overexpression was found in AHH-1 cells treated with 1,4-BQ and while interference with lncRNA-OBFC2A, the expression of Cyclin D1 were reversed. Further, we found that lncRNA-OBFC2A can interact with Smad3 to control cell cycle via modulating Cyclin D1 expression. In benzene exposed workers, the expression of lncRNA-OBFC2A and Smad3 increased while cyclin D1 decreased which was consistent with the in vitro experiment, meanwhile, the significant associations among them were also found. Thus, these findings indicate that lncRNA-OBFC2A targeted to Smad3 regulated cyclin D1 influences cell cycle arrest induced by 1,4-BQ. LncRNA-OBFC2A, Smad3 and Cyclin D1 as a set of biomarkers play important roles in benzene haematotoxicity.

中文翻译：

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靶向 Smad3 调节的细胞周期蛋白 D1 的 lncRNA-OBFC2A 影响 1,4-苯醌诱导的细胞周期停滞

长期接触苯与白血病等不良健康影响有关。据报道，异常的细胞周期进程参与了肿瘤发生。我们之前的研究发现 lncRNA-OBFC2A 通过调节细胞增殖参与苯毒性。然而，lncRNA-OBFC2A在细胞周期调控中的作用尚不清楚，其确切机制有待探索。体外研究表明，苯代谢的 1,4-苯醌 (1,4-BQ) 在 G1 期诱导细胞周期停滞，并以剂量​​依赖性方式降低细胞周期蛋白 D1 的表达。有趣的是，在用 1,4-BQ 处理的 AHH-1 细胞中发现 lncRNA-OBFC2A 过度表达，当干扰 lncRNA-OBFC2A 时，细胞周期蛋白 D1 的表达被逆转。更多，我们发现 lncRNA-OBFC2A 可以与 Smad3 相互作用，通过调节细胞周期蛋白 D1 的表达来控制细胞周期。在苯暴露工人中，lncRNA-OBFC2A和Smad3的表达增加而细胞周期蛋白D1的表达减少，这与体外实验一致，同时也发现它们之间存在显着关联。因此，这些发现表明靶向 Smad3 调节的细胞周期蛋白 D1 的 lncRNA-OBFC2A 影响由 1,4-BQ 诱导的细胞周期停滞。LncRNA-OBFC2A、Smad3 和细胞周期蛋白 D1 作为一组生物标志物在苯血液毒性中起重要作用。还发现了它们之间的重要关联。因此，这些发现表明靶向 Smad3 调节的细胞周期蛋白 D1 的 lncRNA-OBFC2A 影响由 1,4-BQ 诱导的细胞周期停滞。LncRNA-OBFC2A、Smad3 和细胞周期蛋白 D1 作为一组生物标志物在苯血液毒性中起重要作用。还发现了它们之间的重要关联。因此，这些发现表明靶向 Smad3 调节的细胞周期蛋白 D1 的 lncRNA-OBFC2A 影响由 1,4-BQ 诱导的细胞周期停滞。LncRNA-OBFC2A、Smad3 和细胞周期蛋白 D1 作为一组生物标志物在苯血液毒性中起重要作用。