Nasopharyngeal carcinoma (NPC) is one of the Epstein-Barr virus (EBV)-associated malignancies and has a distinct geographical distribution. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for biomarkers for early diagnosis and effective treatments. In this study, we developed DNA aptamers that specifically bind to EBV positive NPC cells by the Cell-SELEX procedure. We further identified the EphA2 (ephrin type-A receptor 2)/CD98hc (CD98 heavy chain) complex as the potential target of the aptamer EA-3 by combining aptamer-based separation and mass spectrometry analysis. Our results revealed for the first time that EphA2 colocalized with CD98hc at the plasma membrane and EphA2 coimmunoprecipitated with CD98hc, which may serve as a starting point for exploring the potential functions of the complex of EphA2 and CD98hc in NPCs. Here, we demonstrated that aptamers can be useful for the identification of protein complexes on the surface of cancer cells.
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