Background: Radioresistance greatly hinders the treatment of nasopharyngeal carcinoma (NPC). Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1 ) has been corroborated to participate in diverse cancers, including NPC. Our aim was to investigate the underlying molecular mechanism of PVT1  in NPC radioresistance.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression levels of PVT1 , microRNA (miR)-515-5p  and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA ) in NPC tissues and cells. Cell counting kit-8 (CCK8) assay, colony formation assay and flow cytometry assay were employed to detect cell proliferation, radiosensitivity and apoptosis, respectively. The protein levels of Cyclin D1, B-cell lymphoma 2 associated X (Bax), Cleaved-caspase-3, PIK3CA, protein kinase B (AKT) and phosphorylated AKT (p-AKT) in samples were measured by Western blot. The starBase was used to predict the binding sites between miR-515-5p  and PVT1  or PIK3CA . Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction. Xenograft tumor model was established to investigate the biological role of PVT1  in vivo.
Results: The levels of PVT1  and PIK3CA  were upregulated in NPC tissues and cells, opposite to the expression of miR-515-5p . Knockdown of PVT1  inhibited cell proliferation, radioresistance and promoted cell apoptosis in NPC cells. Meanwhile, PVT1  silencing downregulated Cyclin D1, and upregulated Bax and Cleaved-casp-3 in NPC cells after radiotherapy. Besides, miR-515-5p  interacted with PVT1  and targeted PIK3CA  in NPC cells. Further studies indicated that PVT1  regulated radioresistance via miR-515-5p/PIK3CA  axis and modulated the AKT pathway by interacting with miR-515-5p . Moreover, knockdown of PVT1  suppressed tumor growth in vivo.
Conclusion: Downregulation of PVT1  inhibited proliferation, radioresistance and promoted apoptosis by downregulating PIK3CA  via sponging miR-515-5p  in NPC cells.
Keywords: NPC, PVT1, miR-515-5p, PIK3CA, radioresistance