IL-17A promotes the proliferation of human nasopharyngeal carcinoma cells through p300-mediated Akt1 acetylation

Abstract

Interleukin (IL)-17A is a T helper (Th)17 cell-secreted cytokine that is able to induce various inflammatory responses. There is emerging evidence that IL-17A is generated in the cancer microenvironment of human nasopharyngeal carcinoma (NPC). However, the role of IL-17A in NPC remains unclear. Thus, the present study aimed to examine the direct influence of IL-17A stimulation on the proliferation of human NPC cells and identify the underlying molecular mechanisms. Furthermore, E1A binding protein p300 (p300)-mediated AKT serine/threonine kinase 1 (Akt1) acetylation and its role in regulating the proliferation of NPC cells was investigated. The results of the current study demonstrated that IL-17A stimulation in vitro increased the proliferation of human NPC cells. Furthermore, Akt1 acetylation was identified to be enhanced in human NPC cells induced by IL-17A. Additionally, p300 induction was demonstrated to be required for Akt1 acetylation in human NPC cells following exposure to IL-17A. Functionally, p300-mediated Akt1 acetylation contributed to the proliferation of human NPC cells stimulated by IL-17A. In conclusion, the results of the present demonstrate a novel activity of IL-17A that promotes human NPC cell proliferation via p300-mediated Akt1 acetylation. This may provide a potential strategy for the treatment of patients with NPC through the inhibition of IL-17A or its receptors.

Interleukin-17F Has Anti-Tumor Effects in Oral Tongue Cancer

“…Similar trends were seen in the low-invasive SCC-25 cells, however, the differences were not significant (Figure 2C,D). Since an opposite effect has been reported for IL-17A (which shares the highest homology with IL-17F) on cancer cells [20], we also investigated the influence of this cytokine on OTSCC cell proliferation. As expected, IL-17A yielded the opposite effect to IL-17F and slightly induced the cell proliferation of both HSC-3 (Figure 2E,F) and SCC-25 (Figure 2G,H), although this did not reach statistical significance.…”

“…IL-17A, which shares the greatest homology with IL-17F, induces apoptosis in distinct cell lines such as oligodendrocytes and neural stem cells when added to culture [28,29]. However, it was also recently reported that IL-17A induces the proliferation of nasopharyngeal carcinoma cell lines [20]. Furthermore, it has been suggested that IL-17A plays a critical role in promoting hyperproliferation in squamous cell carcinomas through the induction of STAT3 and its regulated oncogenic and antiapoptotic gene expression [30].…”

“…IL-17F, the newest member of the IL-17 family that shares the greatest homology with IL-17A, was reported to provide protective effects against several types of cancer, such as oral, colon, and hepatocellular carcinoma [15,16,17,18,19]. It is believed that this anti-tumor effect is mediated via different and complex mechanisms, including influencing cell cycle arrest and inhibition of angiogenesis [15,17,20]. Furthermore, we showed in our recent multicenter study that MC-derived extracellular (rather than intracellular) IL-17F at the cancer invasion front correlates with better disease-specific survival in OTSCC patients [19].…”

Identification of DTL as Related Biomarker and Immune Infiltration Characteristics of Nasopharyngeal Carcinoma via Comprehensive Strategies

“…37,38 IL17A stimulation increased the proliferation of human NPC cells in vitro. 39 Besides, the top five KEGG terms with inverted gene set enrichment included viral protein interaction with cytokine and cytokine receptor, ovarian steroidogenesis, arachidonic acid metabolism and TNF signaling pathway were also related to NPC pathology. The enrichment pathways of GSEA showed that cell cycle, DNA replication, ECM receptor interaction and P53 signaling pathway were highly active in NPC tissue, and the hyperactivity of these pathways may be associated with the development and progression of NPC.…”

Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and alters gene expression during ischemic injury

“…The present study used a cell culture model of ischemic injury to examine the effects of SX on mitochondrial membrane potential and the expression of genes associated with membrane structures and signals, namely adenylyl cyclase (Adcy), adrenoceptor β1 (Adrb1), ATPase Na+/K+ transporting subunit β2 (Atp1b2), calcium voltage-gated channel auxiliary subunit α2δ (Cacna2d)2, Cacna2d3, calcium channel voltage-dependent γ subunit 8 (Cacng8), cytochrome C oxidase subunit 6A2 (Cox6a2), Gnas, phospholipase A2 group 4A (Pla2g4a) and ryanodine receptor 2 (Ryr2) ( 12 – 14 ). In addition, the expression of genes associated with cell proliferation, namely Akt1, fibroblast growth factor receptor (Fgfr)4, 8 and 12, glycogen synthase kinase 3β (Gsk3b), mitogen-activated protein kinase (Mapk)11-14, Mapk kinase kinase kinase 1 (Map4k1), Mas1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (Pik3ca) was evaluated ( 15 – 17 ). Furthermore, genes associated with NO-associated muscle relaxation, including nitric oxide synthase 3 (Nos3) and rap guanine nucleotide exchange factor 4 (Rapgef4), were investigated ( 18 , 19 ).…”