RESUMEN
OBJECTIVE: MiR-506 has been reported to be associated with multiple malignancies, but its roles in nasopharyngeal cancer (NPC) are not fully understood. Our objective is to demonstrate its effects on NPC and the underlying mechanisms. METHODS: Totally fifteen pairs of NPC and adjacent non-tumorous tissues were collected for the detection of miR-506 and enhancer of zeste homolog 2 (EZH2) expression. Dual luciferase reporter assay was employed for verifying the relationship between miR-506 and EZH2. The flow cytometry and MTT assays were employed to explore the effects of miR-506 and EZH2 on the cell apoptosis and proliferation, respectively. Wound closure and transwell assays were used to evaluate the cell migration and invasion abilities. Western blotting or RT-qPCR assays were applied to detect the alterations of miR-506, EZH2 and epithelial-mesenchymal transition (EMT)-related markers. Morphological changes of cells with EMT were assessed by light microscopy. RESULTS: MiR-506 was significantly decreased and EZH2 was obviously increased in NPC tissues. Overexpression of miR-506 decreased the EZH2 level, promoted apoptosis, inhibited proliferation, invasion and migration of NPC cells. Accordingly, miR-506 overexpression attenuated EMT process of NPC cells as demonstrated by the alterations of EMT-related markers and the morphological changes. In addition, the luciferase assay proved that miR-506 directly targeted EZH2. Furthermore, the overexpression of EZH2 reversed the tumor-suppressive effects induced by miR-506 mimics. CONCLUSION: MiR-506 acted as a tumor suppressor to promote apoptosis and inhibit invasion and migration via directly targeting EZH2. MiR-506 can be a candidate target for gene therapy against NPC.
Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/genética , MicroARNs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Transición Epitelial-Mesenquimal/genética , Humanos , MicroARNs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are regarded as a novel population of lineage-negative cells that induce innate Type 2 responses by producing the critical Th2-type cytokines interleukin (IL)-5 and IL-13. ILC2s as key players in the development of allergic rhinitis (AR) have been proved, however, the effect of subcutaneous immunotherapy (SCIT) with dermatophagoides pteronyssinus extract (Der p-SCIT) on ILC2s in AR patients is not clear. This study aimed to investigate the response of ILC2s of peripheral blood in house dust mites (HDM)-sensitized Chinese patients with AR who received SCIT with Der P extract. METHODS: Seven healthy controls without symptoms of AR who had negative reactions to any of the allergens from skin-prick testing, nine patients diagnosed with persistent AR according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, and 24 AR patients who received Der p-SCIT for 1.0-3.5 years were recruited for the study. ILC2s in the peripheral blood were evaluated using flow cytometry. The severity of their symptoms of all participants was rated based on the Total 5 symptom score. RESULTS: Among 40 participants, 9 AR patients were assigned to the untreated group, 24 AR patients receiving Der p-SCIT were assigned to the immunotherapy group, and 7 healthy controls without symptoms of AR were assigned to healthy control group. The mean Total 5 symptom score of immunotherapy group was significantly lower than that of untreated group (4.3 ± 1.4 vs. 10.1 ± 2.5, P< 0.001). Similarly, the levels of ILC2s in the peripheral blood of immunotherapy group were significantly reduced compared with that in untreated group (P < 0.001), but were not significantly different from healthy controls (P = 0.775). Further subgroup analysis based on the duration of SCIT therapy (1.0-2.0 years [SCIT1-2], 2.0-3.0 years [SCIT2-3], and 3.0-3.5 years [SCIT3-3.5]) showed that the percentage of ILC2s was not significantly different between SCIT1-2, SCIT2-3, and SCIT3-3.5groups (SCIT1-2 vs. SCIT2-3: P = 0.268; SCIT1-2vs. SCIT3-3.5: P = 0.635; and SCIT2-3 vs. SCIT3-3.5: P = 0.787). CONCLUSIONS: The present study highlighted the suppression of Der p-SCIT on ILC2s in HDM-AR patients. ILC2s identified in peripheral blood can be used as an effective biomarker for Der p-SCIT.