Chen et al. 2021 (PRJNA755296)

General Details

Title Next Generation Sequencing identifies differentially translated genes regulated by PM2.5 exposure in BEAS-2B cells [Ribo-seq]
Organism
Number of Samples 6
Release Date 2021/08/16 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP332718
ENA SRP332718
GEO GSE182200
BioProject PRJNA755296

Publication

Title
Authors Chen Q, Wang Y, Yang L, Sun L, Wen Y, Huang Y, Gao K, Yang W, Bai F, Ling L, Zhou Z, Zhang X, Xiong J, Zhai R
Journal Journal of experimental & clinical cancer research : CR
Publication Date 2022 Jul 22
Abstract Airborne fine particulate matter (PM2.5) has been associated with lung cancer development and progression in never smokers. However, the molecular mechanisms underlying PM2.5-induced lung cancer remain largely unknown. The aim of this study was to explore the mechanisms by which PM2.5 regulated the carcinogenesis of non-small cell lung cancer (NSCLC). Paralleled ribosome sequencing (Ribo-seq) and RNA sequencing (RNA-seq) were performed to identify PM2.5-associated genes for further study. Quantitative real time-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC) were used to determine mRNA and protein expression levels in tissues and cells. The biological roles of PM2.5 and PM2.5-dysregulated gene were assessed by gain- and loss-of-function experiments, biochemical analyses, and Seahorse XF glycolysis stress assays. Human tissue microarray analysis and 18 F-FDG PET/CT scans in patients with NSCLC were used to verify the experimental findings. Polysome fractionation experiments, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay were implemented to explore the molecular mechanisms. We found that PM2.5 induced a translation shift towards glycolysis pathway genes and increased glycolysis metabolism, as evidenced by increased L-lactate and pyruvate concentrations or higher extracellular acidification rate (ECAR) in vitro and in vivo. Particularly, PM2.5 enhanced the expression of glycolytic gene DLAT, which promoted glycolysis but suppressed acetyl-CoA production and enhanced the malignancy of NSCLC cells. Clinically, high expression of DLAT was positively associated with tumor size, poorer prognosis, and SUVmax values of 18 F-FDG-PET/CT scans in patients with NSCLC. Mechanistically, PM2.5 activated eIF4E, consequently up-regulating the expression level of DLAT in polysomes. PM2.5 also stimulated transcription factor Sp1, which further augmented transcription activity of DLAT promoter. This study demonstrated that PM2.5-activated overexpression of DLAT and enhancement in glycolysis metabolism contributed to the tumorigenesis of NSCLC, suggesting that DLAT-associated pathway may be a therapeutic target for NSCLC. © 2022. The Author(s).
PMC PMC9308224
PMID 35869499
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR15480788 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
SRR15480789 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
SRR15480790 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
SRR15480791 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
SRR15480792 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
SRR15480793 PRJNA755296 Homo sapiens BEAS-2BNA_epithelial cell Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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