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Epithelial-mesenchymal transition markers screened in a cell-based model and validated in lung adenocarcinoma
- Source :
- BMC Cancer, BMC Cancer, Vol 19, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Background Re-capture of the differences between tumor and normal tissues observed at the patient level in cell cultures and animal models is critical for applications of these cancer-related differences. The epithelial-mesenchymal transition (EMT) process is essential for tumor migratory and invasive capabilities. Although plenty of EMT markers are revealed, molecular features during the early stages of EMT are poorly understood. Methods A cell-based model to induce lung cell (A549) EMT using conditioned medium of in vitro cancer activated fibroblast (WI38) was established. High-throughput sequencing methods, including RNA-seq and miRNA-seq, and advanced bioinformatics methods were used to explore the transcriptome profile transitions accompanying the progression of EMT. We validated our findings with experimental techniques including transwell and immunofluorescence assay, as well as the TCGA data. Results We have constructed an in vitro cell model to mimic the EMT in patients. We discovered that several new transcription factors were among the early genes (3 h) to respond to cancer micro-environmental cues which could play critical roles in triggering further EMT signals. The early EMT markers also included genes encoding membrane transporters and blood coagulation function. Three of the nine-examined early EMT hallmark genes, GALNT6, SPARC and HES7, were up-regulated specifically in the early stages of lung adenocarcinoma (LUAD) and confirmed by TCGA patient transcriptome data. In addition, we showed that miR-3613, a regulator of EGFR pathway genes, was constantly repressed during EMT progress and indicative of an epithelial miRNA marker. Conclusions The CAF-stimulated EMT cell model may recapture some of the molecular changes during EMT progression in clinical patients. The identified early EMT hallmark genes GALNT6, SPARC and HES7and miR-3613 provide new markers and therapeutic targets for LUAD for the further clinical diagnosis and drug screening. Electronic supplementary material The online version of this article (10.1186/s12885-019-5885-9) contains supplementary material, which is available to authorized users.
- Subjects :
- Lung adenocarcinoma
0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Cell
Cell Culture Techniques
Fluorescent Antibody Technique
Adenocarcinoma of Lung
RNA-Seq
Biology
lcsh:RC254-282
Transcriptome
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
microRNA
Biomarkers, Tumor
Genetics
medicine
Humans
Gene Regulatory Networks
Epithelial–mesenchymal transition
Transcription factor
Early Detection of Cancer
WGCNA
Gene Expression Profiling
EMT
miRNA-seq
Computational Biology
High-Throughput Nucleotide Sequencing
Cancer
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Gene Expression Regulation, Neoplastic
Gene Ontology
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
embryonic structures
Cancer research
Adenocarcinoma
RNA-seq
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....abc40d1d040da36cfafb9309d470c362