The permissive role of TCTP in PM2.5/NNK-induced epithelial–mesenchymal transition in lung cells

• Published in: Journal of translational medicine 2020-02, Vol.18 (Suppl 1), p.1-17, Article 66
• Main Authors: Liu, Li-Zhong, Wang, Menghuan, Xin, Qihang, Wang, Bowen, Chen, George G, Li, Ming-Yue
• Format: Article
• Language: English
• Subjects: Air pollution; Biological markers; Cancer cells; Cancer metastasis; Carcinogens; Development and progression; Diseases; DNA methylation; Epithelial–mesenchymal transition (EMT); Experiments; Genes; Genetic aspects; Genetic markers; Health aspects; Laboratories; Lung cancer; Lung carcinogens PM2.5/NNK; Mesenchyme; Metastases; Methylation; MicroRNA; MicroRNAs; miRNA; Non-small cell lung cancer; Non-small cell lung carcinoma; Particulate matter; Protein research; Proteins; Small cell lung cancer; Small cell lung carcinoma; Smoking; Statistical analysis; Stem cells; Survival analysis; Therapeutic applications; Time; Translationally controlled tumor protein (TCTP); Tumors; Vimentin; Xenografts
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02256-5

Background Translationally controlled tumor protein (TCTP) is linked to lung cancer. However, upon lung cancer carcinogens stimulation, there were no reports on the relationship between TCTP and lung cell carcinogenic epithelial-mesenchymal transition (EMT). This study was designed to investigate the molecular mechanism of regulation of TCTP expression and its role in lung carcinogens-induced EMT. Methods To study the role of TCTP in lung carcinogens [particulate matter 2.5 (PM.sub.2.5) or 4-methylnitrosamino-l-3-pyridyl-butanone (NNK)]-induced EMT, PM.sub.2.5/NNK-treated lung epithelial and non-small cell lung cancer (NSCLC) cells were tested. Cell derived xenografts, human lung cancer samples and online survival analysis were used to confirm the results. MassArray assay, Real-time PCR and Reporter assays were performed to elucidate the mechanism of regulation of TCTP expression. All statistical analyses were performed using GraphPad Prism version 6.0 or SPSS version 20.0. Results Translationally controlled tumor protein and vimentin expression were up-regulated in PM.sub.2.5/NNK-treated lung cells and orthotopic implantation tumors. TCTP expression was positively correlated with vimentin in human NSCLC samples. Patients with high expression of TCTP displayed reduced overall and disease-free survival. TCTP overexpression could increase vimentin expression and promote cell metastasis. Furthermore, PM.sub.2.5/NNK stimulation brought a synergistic effect on EMT in TCTP-transfected cells. TCTP knockdown blocked PM.sub.2.5/NNK carcinogenic effect. Mechanically, PM.sub.2.5/NNK-induced TCTP expression was regulated by one microRNA, namely miR-125a-3p, but not by methylation on TCTP gene promoter. The level of TCTP was regulated by its specific microRNA during the process of PM.sub.2.5/NNK stimulation, which in turn enhanced vimentin expression and played a permissive role in carcinogenic EMT. Conclusions Our results provided new insights into the mechanisms of TCTP regulatory expression in lung carcinogens-induced EMT. TCTP and miR-125a-3p might act as potential prognostic biomarkers and therapeutic targets for NSCLC. Keywords: Lung carcinogens PM.sub.2.5/NNK, Translationally controlled tumor protein (TCTP), Epithelial-mesenchymal transition (EMT), vimentin, microRNA