Role of inflammation in the malignant transformation of pleural mesothelial cells induced by multi-walled carbon nanotubes

Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma

“… 15 , 57 , 58 An amplified inflammatory response was subsequently stimulated to promote cell proliferation, migration, invasion, colony formation of mesothelial cells. 13 Tkach et al observed that exposure to SWCNTs for one day and seven days facilitated the recruitment of dendritic cells to the lung. 56 Beyeler et al detected that the frequencies of pulmonary dendritic cells were increased following the MWCNT treatment.…”

“…Thus, identification of biomarkers for surveillance of occupational workers to prevent the onset of CNT-induced MPM may be of great clinical significance. However, current studies on the molecular mechanisms of CNT-induced MPM remain rare 12,13,17 and no studies linked CNT-exposed in vitro and in vivo models with MPM patient samples as reports for lung cancer. 26,35 In the present study, we, for the first time, attempted to screen concordant genes differentially expressed both in CNT-exposed MeT5A cells and mice compared with controls and validate the expression, diagnostic and prognostic Based on WGCNA and PPI network analyses, 20 genes were considered as hub module genes associated with the development of CNT-induced MPM.…”

“…12 Huang et al reported that exposure to MWCNTs (0.1 μg/mL) for three months significantly increased the proliferation, migration, invasion and colony-forming abilities of MeT5A cells. 13 Transcriptome sequencing, quantitative polymerase chain reaction (qPCR) and Western blot analyses revealed activation of the nuclear factor kappa B (NF-κB)/interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) inflammatory pathway may be an important mechanism in MWCNT-induced malignant transformation of MeT5A cells; silencing of these pathway genes reversed the above malignant phenotypes of MeT5A cells. 13 Macrophage co-culture [13][14][15] and rat/ mouse peritoneal cavity injection 14,16 experiments demonstrated MWCNTs may induce the development of MPM by stimulating the macrophage accumulation, which then enhanced the production of NF-κB, IL-6, IL-1β, tumor necrosis factor-α (TNF-α) and STAT3 of mesothelial cells.…”

“…13 Transcriptome sequencing, quantitative polymerase chain reaction (qPCR) and Western blot analyses revealed activation of the nuclear factor kappa B (NF-κB)/interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) inflammatory pathway may be an important mechanism in MWCNT-induced malignant transformation of MeT5A cells; silencing of these pathway genes reversed the above malignant phenotypes of MeT5A cells. 13 Macrophage co-culture [13][14][15] and rat/ mouse peritoneal cavity injection 14,16 experiments demonstrated MWCNTs may induce the development of MPM by stimulating the macrophage accumulation, which then enhanced the production of NF-κB, IL-6, IL-1β, tumor necrosis factor-α (TNF-α) and STAT3 of mesothelial cells. In the study of Chernova et al, the expression levels of STAT3, IL-6 and phosphatidylinositol 3-kinase (PI3K) genes were identified to be increased, while cyclin dependent kinase inhibitor 2A (CDKN2A) was shown to be decreased in CNT-induced MPM lesions at 6 months postinjection.…”

“…The functions of hub genes were predicted by linking to the infiltration levels of various immune cells since inflammation seemed to be an important contributor for CNT-associated MPM. [13][14][15]…”