RESUMEN
Radioresistance remains a challenge during nasopharyngeal carcinoma (NPC) radiotherapy. Numerous studies suggest that the miRNAs may play important roles in the regulation of radioresistance. miRNA-17-5p, which is located within the miR-17-92a cluster, could modulate tumor progression in different tissues by targeting multiple tumor associated genes. However, whether it is correlated with the radioresistance of tumor cells has not yet been elucidated. In our study, we have observed increasing miR-17-5p expression in radioresistant NPC tissues. The functional experiments suggested that miR-17-5p could clearly promote NPC cell proliferation and the cell cycle even after X-ray irradiation. Irradiation leads to tumor cell damage and death via ROS generation. The overexpression of miR-17-5p could protect NPC cells from apoptosis induced by irradiation. In addition, an in vivo experiment indicated that miR-17-5p promoted tumor growth with radiotherapy using the xenograft tumor model. A bioinformatics analysis and reporter assay were carried out to demonstrate that PTEN, which is a key regulator of AKT phosphorylation, is a target of miR-17-5p. The overexpression of miR-17-5p directly suppresses the mRNA and protein expression of PTEN. In addition, the rescue experiments showed that the AKT inhibitor can diminish the proliferation, promotion, and apoptosis inhibition effects on radioresistant NPC cells mediated by miR-17-5p. In conclusion, our findings demonstrated that miR-17-5p can enhance the radioresistance of NPC through the PTEN/AKT pathway, which is a biomarker of radioresistant NPC and a potential target for new therapeutic strategies.
RESUMEN
In nasopharyngeal carcinoma (NPC), the nuclear factor-κB (NF-κB) signaling pathway is highly active. The constitutive activation of NF-κB prompts malignant cell proliferation, and microRNAs are considered an important mediator in regulating the NF-κB signaling pathway. The current study investigated the effect of microRNA-200a (miR-200a) on NF-κB activation. Reverse transcription-quantitative polymerase chain reaction was used to quantify the relative level of miR-200a in NPC tissue samples and CNE2 cells. An MTT assay was used to investigate the effect of miR-200a on cell proliferation. To investigate the activation of NF-κB, western blotting was used to measure the protein levels of NF-κB and its downstream targets. To identify the target genes of miR-200a, a luciferase reporter assay was used. The current study demonstrated that miR-200a was upregulated in NPC tissue samples and cell lines. Overexpression of miR-200a resulted in the proliferation of CNE2 cells. Western blot analysis indicated that the protein levels of p65 increased when CNE2 cells were transfected with miR-200a mimics. Additionally, the downstream targets of miR-200a were upregulated, including vascular cell adhesion molecule, intercellular adhesion molecule and monocyte chemoattractant protein-1. The luciferase assay indicated that IκBα was the target gene of miR-200a. In conclusion, miR-200a was demonstrated to enhance NPC cell proliferation by activating the NF-κB signaling pathway.
