Abstract
BackgroundRadioresistance is a major challenge during the treatment of NK/T cell lymphoma. This study aimed to investigate the potential role of MicroRNA-150 (miR-150) in increase the sensitivities of NK/T cell lymphoma to ionizing radiation.ResultsIn this study, we found that miR-150 was significantly decreased in NK/T cell lymphoma tissues and cell lines. Low expression of miR-150 was positively associated with therapeutic resistance in 36 NK/T cell lymphoma cases. Our further in vitro and in vivo studies illustrated that overexpression of miR-150 substantially enhanced the sensitivity of NK/T cell lymphoma cells to ionizing radiation treatment. Furthermore, luciferase reporter assays in NK/T cell lymphoma cells transfected with the AKT2 or AKT3 three prime untranslated region reporter constructs established AKT2 and AKT3 as direct targets of miR-150. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit Akt to verify miR-150 increase NK/T cell lymphoma cell radiorsensitivity through suppress the PI3K/AKT/mTOR pathway.ConclusionsTaken together, this study demonstrates that miR-150 might serve as a potential therapeutic sensitizer through inhibition of the AKT pathway in NK/T cell lymphoma treatment.
Highlights
Radioresistance is a major challenge during the treatment of NK/T cell lymphoma
The response of radiotherapy was assessed clinically for primary lesion based on CT and PET/CT 1 month after treatment according to the following criteria: complete response (CR) was defined as the complete disappearance of all assessable lesions, partial response (PR) was defined as a reduction of the sum of the lesions by 50% or more and no progression of assessable lesions, stable disease (SD) was indicated by a reduction of < 50% or an increase of < 25% in tumor size
MiR-150 expression was positively correlated with the treatment response of NK/T cell lymphoma (NKTL) patients As shown in Table 1, low expression of miR-150 was closely correlated with the viral load of Epstein-Barr virus (EBV) (EBV ≧ 50 copy/ml severse as positive)
Summary
Radioresistance is a major challenge during the treatment of NK/T cell lymphoma. This study aimed to investigate the potential role of MicroRNA-150 (miR-150) in increase the sensitivities of NK/T cell lymphoma to ionizing radiation. NK/T cell lymphoma (NKTL) is diagnosed more commonly in Asia and Latin America than in Western countries and accounts for 5–10% of all malignant lymphomas in China [1, 2]. Radiotherapy is usually regarded as the main treatment, the cellular response to irradiation is complex. The treatment effects depend on many factors. One of the main causes of failure in radiotherapy is radioresistance [3,4,5]. To develop effective radiotherapy strategies in the future, the knowledge of how radioresistance develops at the molecular level is needed
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