Benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15.

Pengling Sun,Yujiao Chen,Xiaoli Guo,Ai Gao,Caihong Xing,Jing Wang

doi:10.18632/oncotarget.16588

Pengling Sun, Yujiao Chen + Show 4 more

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https://doi.org/10.18632/oncotarget.16588

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Abstract

LncRNA has been considered to play a crucial role in the progression of several diseases by affecting cell proliferation. However, its role in benzene toxicity remains unclear. Our study showed that the expression of lncRNA-OBFC2A increased accompanied with the change of cell proliferation related-genes in benzene-exposed workers. In vitro experiments, 1,4-Benzoquinone dose-dependently inhibited cell proliferation and simultaneously caused the decrease of NOTCH1 expression and the increase of KLF15 in AHH-1 cell lines. Meanwhile, 1, 4-Benzoquinone obviously increased the expression of lncRNA-OBFC2A, which was consistent with our previous population results. Therefore, we propose that lncRNA-OBFC2A is involved in benzene toxicity by regulating cell proliferation. Further, we successfully constructed a lentivirus model of interfering the expression of lncRNA-OBFC2A. After interfering lncRNA-OBFC2A, the cell proliferation inhibition and the expression of NOTCH1 and KLF15 induced by 1, 4-Benzoquinone were reversed. Subsequently, RNA fluorescence in situ Hybridization assay showed that lncRNA-OBFC2A was located in cell nuclei. These results suggest that benzene and its metabolite decreases cell proliferation via LncRNA-OBFC2A-mediated anti-proliferation effect involving NOTCH1 and KLF15. LncRNA-OBFC2A can be a potential biomarker for benzene toxicity.

Highlights

Benzene, a significant organic solvent and industrial raw materials, widely exists in the production environment and living environment, especially in developing countries [1]
Growing studies have shown that many lncRNA molecules are associated with the leukemia [23]
The results showed that lncRNA-OBFC2A increased in benzene-exposed workers and there was a close correlation between lncRNAOBFC2A and cell proliferation related-genes

Summary

Introduction

A significant organic solvent and industrial raw materials, widely exists in the production environment and living environment, especially in developing countries [1]. Workers exposed to benzene in China are more than 50 million. Nausea, coma, organ (e.g., liver and kidney) failure, or an occurrence of blood diseases if an excessive amount of benzene is inhaled over a short period [2, 3]. In 1982, IARC formally designated benzene to be a human carcinogen. Many domestic and foreign scholars have made a lot of research, but the mechanism of benzene poisoning is not completely clear. There is no effective treatment on benzene poisoning. There is still lack of a useful marker for benzene health care and risk screening

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