Research Paper Volume 13, Issue 19 pp 23119—23132
Ribosome profiling reveals translatome remodeling in cancer cells in response to zinc oxide nanoparticles
- 1 Sir Run-Run Shaw Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China
- 2 Key Laboratory of Endoscopic Technique Research of Zhejiang Province, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
- 3 Department of Urology, Shaoxing Branch of Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Shaoxing 312000, China
- 4 Department of Occupational Health and Radiation Protection, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang, China
- 5 Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
Received: August 7, 2021 Accepted: September 20, 2021 Published: October 7, 2021
https://doi.org/10.18632/aging.203606How to Cite
Copyright: © 2021 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.