MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis

Abstract

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.

Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

“…MiR-222 interacts with PTEN in NPC cells, resulting in elevated cell proliferation, colony formation and finally radiation resistance [163]. Additionally, miR-19b-3p can decrease sensitivity to irradiation in vitro and in vivo by activating the TNFAIP3/NF-κB pathway, which might serve as a potential therapeutic point in NPC treatment [164]. Taken together, miRNAs play controversial roles in response to radiation, and it is possible that by targeting some core miRNAs, patients with NPC can develop less resistance and benefit more from radiotherapy.…”

LINC00961 inhibits the migration and invasion of colon cancer cells by sponging miR‐223‐3p and targeting SOX11

“…Transwell migration and invasion assay was performed in accordance with previously described methods. 19 For the Transwell migration assays, the transfected HT29 and SW480 (N = 6 × 10 3 ) cells were plated in top chambers with a noncoated membrane. For the invasion assays, the transfected HT29 and SW480 (N = 10 × 10 3 ) cells were plated in top chambers with a coated membrane.…”

Decrease of miR-19b-3p in Brain Microvascular Endothelial Cells Attenuates Meningitic Escherichia coli-Induced Neuroinflammation via TNFAIP3-Mediated NF-κB Inhibition

“…An earlier study pointed to TNFAIP3 as one of the potential targets of miR-19b-3p [23]. Since miR-19b-3p was shown to be involved in meningitic E. coli infection, whether it also functioned through TNFAIP3 was unclear and needed to be further revealed.…”