Tumor necrosis factor ? promotes HEp-2 cell proliferation via toll-like receptor 4 and NF-?B signaling pathways.

ABSTRACT: Laryngeal carcinoma is a serious, life-threatening disease. Tumor necrosis factor ? (TNF-?), a proinflammatory cytokine, has complex effects on the proliferation and growth of cancer cells. Previously, we treated a laryngeal cancer cell line (HEp-2) with TNF-? and demonstrated that this treatment suppressed polycystin-2, a transient receptor potential cation channel expression and ATP-induced Ca2+ release but increased HEp-2 cell proliferation and growth. However, the mechanisms and signaling pathways underlying the TNF-? effects on the HEp-2 cells were unclear. Therefore, we here used RNA-seq techniques to examine the effect of TNF-? on the gene transcript expression profile in these cells. We found that TNF-? treatment (100 ng/mL, 24 h) upregulated 2,811 genes and downregulated 1,128 genes. The IRAK1 gene encoding an effector protein downstream of toll-like receptor 4 (TLR4) was ranked 19th in the upregulated differentially expressed genes. In a gene ontology (GO) analysis, 168 GO terms were identified in the biological process domain for the upregulated differentially expressed genes, and cell cycle and DNA replication functions were enriched. In a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, TNF-? treatment enhanced the NF-?B pathway in HEp-2 cells. Moreover, both the transcript and protein expression levels of TLR4 as well as the expression of genes encoding downstream TLR4 effectors were significantly increased in TNF-?-treated HEp-2 cells. We concluded that TNF-? increased HEp-2 cell proliferation and growth likely via enhancing TLR4- and NF-?B-associated signaling pathways and that TNF-? may play an important role in the development of laryngeal cancer.

SUBMITTER: Yu D 

PROVIDER: S-EPMC6966063 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature