Social Science Research Network | 2021
Competitive Endogenous RNAs Participate in Benzene Hematotoxicity by Promoting Ferroptosis
Abstract
Background: Benzene exposure leads to hematotoxicity, but we still lack sensitive biomarkers for its monitoring and prevention owing to the complex mechanisms. We previously constructed a competitive endogenous RNA(ceRNA) regulatory network (Lnc-TC-miR-142-5p-CUL4B), which may be potential biomarkers for benzene hematotoxicity, and further explored the mechanism of these ceRNAs mediating benzene toxicity. \n \nMethods: Peripheral hemogram and ceRNA expression were detected in benzene-exposed workers and controls. Cell viability, ultrastructural changes, lipid ROS and expressions of cell ferroptosis related genes GPX4, SLC7A11 and FTH were examined to detect the occurrence of benzene metabolite 1, 4-benzoquinone (1,4-BQ)-induced ferroptosis. Lentiviral transfected cell models of regulating Lnc-TC, miR-142-5p and CUL4B were constructed to explore their regulatory relationships and roles in 1,4-BQ induced ferroptosis. \n \nResults: We confirmed that the expression of ceRNAs Lnc-TC-miR-142-5p-CUL4B were significantly changed and associated with decreased blood cell counts in benzene-exposed workers compared with controls. 1,4-BQ promoted cell ferroptosis characterized by mitochondria damages, increased lipid ROS level, and down-regulation of GPX4, SLC7A11 and FTH. Lnc-TC-miR-142-5p-CUL4B ceRNA network regulated 1,4-BQ-induced cell ferroptosis by targeting GPX4, thus participated in benzene hematotoxicity. \n \nConclusion: The Lnc-TC-miR-142-5p-CUL4B ceRNA network mediated benzene hematotoxicity by promoting ferroptosis, and these ceRNAs may be potential biomarkers for early monitoring and warning of disease. \n \nFunding Information: This research was supported by the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201810025032), the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan (CIT&TCD20170323) and National Culture Science Foundation of China (81773397). \n \nDeclaration of Interests: The authors of this article declare that there are no conflicts of interest. \n \nEthics Approval Statement: The study was approved by Ethics committee of Capital Medical University, each individual signed an informed consent form.