Ribosome profiling reveals translatome remodeling in cancer cells in response to zinc oxide nanoparticles

The anticancer effect of zinc oxide nanoparticles (ZnO NPs) largely relies on cellular responses such as alteration of gene expression. Although ZnO NPs have been reported to induce transcriptional changes, the potential of ZnO NPs to affect cellular translatome remains largely unknown. Using ribosome profiling, we demonstrated that the transcription of 78 genes and the translation of 1,448 genes are affected during one hour of ZnO NPs exposure in A549 human lung cancer cells. The mitogen- activated protein kinase (MAPK) pathway is up-regulated upon ZnO NP treatment. The upstream open reading frame (uORF) plays a pervasive role in the induction of up- regulated genes, including TLNRD1 and CCNB1IP1. Knockdown of TLNRD1 or CCNB1IP1 reduces ZnO NP-induced cytotoxicity. Together, our study characterizes the landscape of translational alteration under ZnO NPs treatment and provides potential targets to augment the anticancer effect of ZnO NPs.

Automated summary

Our study reveals that zinc oxide nanoparticles (ZnO NPs) affect the transcription of 78 genes and translation of 1,448 genes in A549 human lung cancer cells within one hour of exposure. The mitogen-activated protein kinase (MAPK) pathway is up-regulated upon ZnO NP treatment, and upstream open reading frame (uORF) plays a crucial role in the induction of up-regulated genes such as TLNRD1 and CCNB1IP1, which in turn reduces ZnO NP-induced cytotoxicity. This study characterizes the landscape of translational alteration under ZnO NPs treatment and identifies potential targets to enhance the anticancer effect of ZnO NPs.