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

Saisai Wei,Wenhao Guo,Xiangwei Gao,Kangli Liu,Yicheng Chen,Jie Xiang,Xiang-Jing Gao,Yu Qian

doi:10.18632/aging.203606

Saisai Wei, Wenhao Guo + Show 6 more

Open Access

https://doi.org/10.18632/aging.203606

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Abstract

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.

Highlights

Nanotechnology has made remarkable progress in recent years
In the current study, using ribosome profiling, we demonstrated that 1 hour of ZnO nanoparticles (ZnO NPs) treatment induced dramatic mRNA translation changes www.aging-us.com in A549 cells
We identified a series of ZnO NPs-responsive genes, including TLNRD1 and CCNB1IP1, that promote cancer cell death under ZnO NPs treatment

Summary

Introduction

Nanotechnology has made remarkable progress in recent years. Due to their unique physical and chemical characteristics, nanoparticles (NPs) are progressively being used for various industrial/household applications as well as clinical purposes [1]. It was reported that cancer cells are more sensitive to ZnO NPs treatment than normal cells [4]. Oxidative stress is the leading cause of ZnO NP-induced cancer cell toxicity [1]. In response to ZnO NP-induced oxidative stress, cells alter gene expression, which regulates cytotoxicity of ZnO NPs. mRNA-sequencing (mRNAseq) studies have provided insights into the transcriptional responses to ZnO NPs [5]. The changes in mRNA abundance are not necessarily predictive of changes at the protein level

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