Investigation of PM2.5-induced carcinogenic effects through mediation of ErbB family based on DNA methylation and transcriptomics analysis by a lung-mimicking microfluidic platform

Lulu Zheng; Yuwen Wang; Yule Zhang; Zongtao Chai; Sixiu Liu; Bo Wang; Bo Dai; Dawei Zhang

doi:10.1016/j.ecoenv.2022.114318

Investigation of PM_2.5-induced carcinogenic effects through mediation of ErbB family based on DNA methylation and transcriptomics analysis by a lung-mimicking microfluidic platform

Ecotoxicol Environ Saf. 2022 Dec 15:248:114318. doi: 10.1016/j.ecoenv.2022.114318. Epub 2022 Nov 25.

Authors

Lulu Zheng¹, Yuwen Wang¹, Yule Zhang¹, Zongtao Chai², Sixiu Liu³, Bo Wang¹, Bo Dai¹, Dawei Zhang⁴

Affiliations

¹ Engineering Research Center of Optical Instrument and System, Ministry of Education, Shanghai Key Lab of Modern Optical System, Shanghai Environmental Biosafety Instruments and Equipment Engineering Technology Research Center, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai 200093, China.
² Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
³ Shanghai Key laboratory of Atmospheric Particle Pollution Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, 220 Handan Road, Shanghai 200433, China.
⁴ Engineering Research Center of Optical Instrument and System, Ministry of Education, Shanghai Key Lab of Modern Optical System, Shanghai Environmental Biosafety Instruments and Equipment Engineering Technology Research Center, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai 200093, China; Shanghai Institute of Intelligent Science and Technology, Tongji University, China. Electronic address: daweizhang@usst.edu.cn.

PMID: 36442402
DOI: 10.1016/j.ecoenv.2022.114318

Abstract

Fine particle (PM_2.5, less than 2.5 micrometers in diameter) is regarded as a harmful carcinogen. However, the molecular mechanisms of the carcinogenic effects of ambient fine particles have not been fully elucidated, and therapeutic options to address this major public health challenge are lacking. Here, we present global gene-specific DNA methylation and transcriptomic (RNA-Seq) analyses after HBE cells were exposed to fine particles on a portable, small, and all-in-one organ-level lung-mimicking air-liquid interface exposure (MALIE) microfluidic platform. A series of cancer-related signal transduction pathways were activated. ErbB1, ErbB2, and ErbB3 gene expression altered by fine particle exposure was the result of changes in the cellular DNA methylome. The protein expression of ErbB family was inhibited by drugs and could regulate downstream Grb2/Raf pathway and Akt/MDM2 pathway. All of the above results indicated that ErbB family may be promising drug targets for air pollution-related diseases and that inhibitor drugs can be used as therapeutic options to treat these diseases.

Keywords: Carcinogenic effects; ErbB family; Inhibitors; Microfluidic chip; PM2.5.

MeSH terms

DNA Methylation*
Lung
Microfluidics*
Particulate Matter / toxicity
Transcriptome

Substances

Particulate Matter