ATF5 involved in radioresistance in nasopharyngeal carcinoma by promoting epithelial-to-mesenchymal phenotype transition.

PURPOSE: This study aimed to investigate the effects of activating transcription factor-5 (ATF5) on nasopharyngeal carcinoma (NPC) cell radioresistance.

METHODS

HONE-1 nasopharyngeal carcinoma cells were irradiated by conventional fractionation to generate HONE-1R radiotherapy-resistant cells. Short hairpin RNA (shRNA) expression plasmids targeting the ATF5 gene were constructed and transfected into the HONE-1R cell line. The proliferation assay, colony formation analysis, Transwell Boyden chamber assay and other experimental methods were performed to verify changes in the radiosensitivity and other biological of NPC cells.

RESULTS

X-ray irradiation significantly promoted the upregulation of ATF5 protein levels in HONE-1 cells, and the protein expression of ATF5 increased with the dose of X-ray irradiation (p < 0.05). The colony formation rate, cell survival rate and migration ability of HONE-1R cells were significantly higher than those of HONE-1 cells (p < 0.05). Simultaneously, X-ray could also promote the morphology of epithelial-mesenchymal transition (EMT) in HONE-1 cells, inducing a lower expression level of E-cadherin and a higher expression level of N-cadherin in a dose-dependent manner (p < 0.05). Inhibiting ATF5 significantly reduced the colony formation rate, cell survival rate, migration and invasiveness of HONE-1R cells (p < 0.05). Moreover, sensitizing HONE-1R cells to X-ray irradiation significantly upregulated the expression of E-cadherin and downregulated the expression of N-cadherin in these cells (p < 0.05).

CONCLUSIONS

ATF5 may be a potential therapeutic target to improve radiosensitivity in NPC.