Exposure to airborne PM2.5 suppresses microRNA expression and deregulates target oncogenes that cause neoplastic transformation in NIH3T3 cells

Oncotarget
Chunling LiuDongxin Lin

Abstract

Long-term exposure to airborne PM2.5 is associated with increased lung cancer risk but the underlying mechanism remains unclear. We characterized global microRNA and mRNA expression in human bronchial epithelial cells exposed to PM2.5 organic extract and integrally analyzed microRNA-mRNA interactions. Foci formation and xenograft tumorigenesis in mice with NIH3T3 cells expressing genes targeted by microRNAs were performed to explore the oncogenic potential of these genes. We also detected plasma levels of candidate microRNAs in subjects exposed to different levels of air PM2.5 and examined the aberrant expression of genes targeted by these microRNAs in human lung cancer. Under our experimental conditions, treatment of cells with PM2.5 extract resulted in downregulation of 138 microRNAs and aberrant expression of 13 mRNAs (11 upregulation and 2 downregulation). In silico and biochemical analyses suggested SLC30A1, SERPINB2 and AKR1C1, among the upregulated genes, as target for miR-182 and miR-185, respectively. Ectopic expression of each of these genes significantly enhanced foci formation in NIH3T3 cells. Following subcutaneous injection of these cells into nude mice, fibrosarcoma were formed from SLC30A1- or SERPINB2-expressin...Continue Reading

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Citations

Sep 24, 2020·CA: a Cancer Journal for Clinicians·Michelle C TurnerAaron Cohen
Aug 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Ming-Yue LiGeorge G Chen
Jan 5, 2021·Environmental Science and Pollution Research International·Xi LuXixin Yan
May 20, 2020·Toxicology Reports·Satheeswaran BalasubramanianEkambaram Perumal
Jul 16, 2021·Ecotoxicology and Environmental Safety·Bixia LiBoguang Wang

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Methods Mentioned

BETA
PCR
transfection
xenograft
electrophoresis
light microscopy

Software Mentioned

Statistical Analysis System
Ingenuity Pathway Analysis ( IPA )
miRanda
TargetScan

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