Lnc-TC/miR-142-5p/CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity.

Exposure to benzene causes damage to the hematopoietic system, but the mechanisms are still unclear. Competitive endogenous RNAs (ceRNAs) are the epigenetic regulatory axis of long non-coding RNA (lncRNA)-microRNA-mRNA, which are shown to play roles in benzene-induced hematotoxicity. Ferroptosis, a lipid peroxidation-dependent cell death, has been reported to be regulated by ceRNAs. We hypothesized that ceRNAs regulated ferroptosis to participate in benzene hematotoxicity. In this study, we observed that the expression of lncRNA TC (Lnc-TC) and CUL4B were increased, but miR-142-5p was decreased in benzene-exposed workers. Correlation analysis suggested that the ceRNAs had co-expression relationships, and were associated with blood cell counts. We further explored the role of ceRNA in vitro, and discovered that 1,4- benzoquinone (1,4-BQ) stimulated ferroptosis in AHH-1 cells by inhibiting the expression of GPX4 and SLC7A11 , which was partially relieved by knockdown of Lnc-TC and CUL4B. Finally, by interfering with Lnc-TC and miR-142-5p expression, we confirmed that Lnc-TC acted as a microRNA sponge to reduce the accessibility and inhibition of miR-142-5p to CUL4B , thus increasing the expression of CUL4B. In summary, Lnc-TC / miR-142-5p / CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity, and was a potential biomarker for risk screening and health surveillance of benzene-exposed workers. [Display omitted] • Benzene induced aberrant expression of Lnc-TC/miR-142-5p/CUL4B network. • Ferroptosis was involved in hematotoxicity of benzene. • Lnc-TC/miR-142-5p/CUL4B network mediated benzene-induced ferroptosis. • Lnc-TC acted as a sponge for miR-142-5p to increase CUL4B expression. [ABSTRACT FROM AUTHOR]