PVT1 Mediates Cell Proliferation, Apoptosis and Radioresistance in Nasopharyngeal Carcinoma Through Regulating miR-515-5p/PIK3CA Axis

• Main Authors: Han Y, Li F, Xie J, Wang Y, Zhang H
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-10-01
• Series: Cancer Management and Research
• Subjects: npc; pvt1; mir-515-5p; pik3ca; radioresistance
• Online Access: https://www.dovepress.com/pvt1-mediates-cell-proliferation-apoptosis-and-radioresistance-in-naso-peer-reviewed-article-CMAR

Yanyan Han,1 Fang Li,2 Jun Xie,2 Yi Wang,2 Hua Zhang1 1Department of Otolaryngology, The First Affiliate Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Otolaryngology, Urumqi Eye and ENT Specialist Hospital, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Hua Zhang Tel [phone]Email [e-mail]: 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