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Series GSE142620 Query DataSets for GSE142620
Status Public on Dec 27, 2019
Title Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis.
Overall design Compare transcriptome profiles between IL-1β treated and control untreated A549 cells at different time points. Each biological condition was represented by triplicate.
Contributor(s) Li R, Ong SL, Tran LM, Jing Z, Huang ZL, Liu B, Lee G, Salehi-Rad R, Krysan K, Pagano PC, Paul MK, Xu S, Herschman HR, Dubinett SM, Park SJ, Walser TC, Heinrich EL, Crosson WP
Citation(s) 31941995
Submission date Dec 26, 2019
Last update date Mar 27, 2020
Contact name Linh My Tran
Organization name University of Los Angeles
Department Medicine - Pulmonary & Critical Care
Lab Dubinett Lab
Street address Box 951690, 37-131 CHS
City Los Angeles
State/province California
ZIP/Postal code 90095-1690
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (36)
GSM4232997 A549_Ctrl_6d_repA
GSM4232998 A549_IL1b_6d_repA
GSM4232999 A549_Ctrl_15d_repA
BioProject PRJNA597764
SRA SRP238840

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE142620_RAW.tar 7.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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