BackgroundNasopharyngeal carcinoma (NPC) is among the most common squamous cell carcinoma in South China and Southeast Asia. Radiotherapy is the primary treatment for NPC. However, radioresistance acts as a significant factor that limits the efficacy of radiotherapy for NPC patients. Growing evidence supports that microRNAs (miRNAs) play an important role in radiation response.MethodsReal-time quantitative PCR was used to analyze the expression of miR-19b-3p in NPC cell lines and NP69. miR-19b-3p expression profiles in NPC tissues were obtained from the Gene Expression Omnibus database. The effect of miR-19b-3p on radiosensitivity was evaluated by cell viability assays, colony formation assays and in vivo experiment. Apoptosis and cell cycle were examined by flow cytometry. Luciferase reporter assay was used to assess the target genes of miR-19b-3p. Expression of target proteins and downstream molecules were analyzed by Western blot.ResultsmiR-19b-3p was upregulated in NPC and served as an independent predictor for reduced patient survival. Radioresponse assays showed that miR-19b-3p overexpression resulted in decreased sensitivity to irradiation, whereas miR-19b-3p downregulation resulted in increased sensitivity to irradiation in vitro. Moreover, miR-19b-3p decreased the sensitivity of NPC cells to irradiation in vivo. Luciferase reporter assay confirmed that TNFAIP3 was a direct target gene of miR-19b-3p. Knockdown of TNFAIP3 reduced sensitivity to irradiation, whereas upregulation of TNFAIP3 expression reversed the inhibitory effects of miR-19b-3p on NPC cell radiosensitivity. Mechanistically, we found that miR-19b-3p increased NPC cell radioresistance by activating the TNFAIP3/ NF-κB axis.ConclusionsmiR-19b-3p contributes to the radioresistance of NPC by activating the TNFAIP3/ NF-κB axis. miR-19b-3p is a determinant of NPC radioresponse and may serve as a potential therapeutic target in NPC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0465-1) contains supplementary material, which is available to authorized users.
Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial‐mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR‐130a‐3p in the progression of transforming growth factor‐β (TGF‐β)‐induced EMT in vivo and in vitro. The expression of miR‐130a‐3p in ESCC cell line and normal esophageal epithelial cell was determined by RT‐qPCR. The protein expression levels of TGF‐β‐induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual‐luciferase report assays were used to validate the regulation of miR‐130a‐3p‐SMAD4 axis. The effect of miR‐130a‐3p and SMAD4 in TGF‐β‐induced migration, invasion in the ESCC cell line EC‐1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF‐β‐induced migration, invasion, and EMT progression in the ESCC cell line EC‐1. miR‐130a‐3p, which directly targets SMAD4, is down‐regulated in ESCC. miR‐130a‐3p inhibits the migration and invasion of EC‐1 cells both in vitro and in vivo. Finally, miR‐130a‐3p inhibits TGF‐β‐induced EC‐1 cell migration, invasion, and EMT progression in a SMAD4‐dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF‐β/miR‐130a‐3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.
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