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.

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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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Background/Aims: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells. Methods: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184. Results: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells. Conclusion: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC.

TNF alpha induced protein 3 (TNFAIP3), a member of zinc finger protein family, is a gene whose expression level is promptly induced by the tumor necrosis factor. In this study, the clinical significance of TNFAIP3 was analyzed based on available samples in The Cancer Genome Atlas database. TNFAIP3 downregulation was associated with distant metastasis and worse patient prognosis. TNFAIP3-overexpressing and TNFAIP3-knockdown NPC cell line models were established through plasmid-mediated overexpression and small interfering RNA (siRNA), respectively. Cell migration and invasion capacities were evaluated by wound-healing and transwell assays. Functional studies indicated that TNFAIP3 knockdown promoted migration and invasion, whereas TNFAIP3 overexpression alleviated these functions. Western blot analysis was used to examine protein changes from TNFAIP3 overexpression and knockdown, in which TNFAIP3 promoted the protein expression of E-cadherin and suppressed vimentin expression. Our data suggested that TNFAIP3 inhibited migration and invasion by suppressing epithelial mesenchymal transition in NPC.

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