Long Non-coding RNA PANDAR Promotes Radioresistance in Nasopharyngeal Carcinoma via SIRT1/Ku70/PI3K/Akt Pathway

Abstract Objective: Radioresistance may result in nasopharyngeal carcinoma (NPC) radiation failure. To comprehend the concrete mechanism in NPC radioresistance, this work was initiated from long non-coding RNA (lncRNA) promoter of CDKN1A antisense DNA damage activated RNA (PANDAR), accompanied by sirtuin 1 (SIRT1), Ku70, and phosphatidylinositol 3 kinase (PI3K)/Akt pathway.Methods: NPC cancer tissues and normal tissues were harvested and NPC cancer tissues were specified into radioresistant and radiosensitive types. The connection between PANDA expression with NPC radioresistance, clinicopathological traits and prognosis was tested. Radioresistant CNE2-IR and 5-8F-IR cells were induced and transfected with depleted PANDAR or SIRT1 to identify their roles in cell proliferation, cycle distribution, apoptosis, SIRT1, Ku70 and PI3K/Akt pathway. PANDA and SIRT1 expression in CNE2-IR and 5-8F-IR cells were tested.Results: PANDA was elevated in NPC tissues and radioresistant tissues relative to normal tissues and radiosensitive tissues. Raised PANDA was connected with NPC radioresistance and unsatisfactory prognosis. CNE2-IR and 5-8F-IR cells expressed up-regulated PANDA and SIRT1. Down-regulating PANDA or SIRT1 inhibited radioresistant NPC cell proliferation, decreased SIRT1 and Ku70, and inactivated PI3K/Akt pathway.Conclusion: This work has clued that depleting PANDA decreases SIRT1 recruitment to inactivate Ku70 deacetylation-mediated PI3K/Akt pathway, thereby promoting NPC radiosensitivity.