BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

Abstract

Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients. We previously generated a cisplatin-sensitive NPC cell line, S16, from CNE2 cells and found that eIF3a, ASNS and MMP19 are upregulated in S16 cells, which contributes to their cisplatin sensitivity. In this study, we found that BST2 is downregulated in cisplatin-sensitive S16 cells compared with CNE2 cells. Knockdown of BST2 in NPC cells sensitized their response to cisplatin and promoted cisplatin-induced apoptosis, whereas exogenous overexpression of BST2 increased their cisplatin resistance and inhibited cisplatin-induced apoptosis. Further investigation demonstrated that BST2-mediated cisplatin resistance depended on the activation of the NF-κB signaling pathway and consequent upregulation of anti-apoptotic genes, such as Bcl-XL and livin. Moreover, an analysis of clinical data revealed that a high BST2 level might serve as an independent indicator of poor prognosis in patients with locally advanced NPC treated with platinum-based chemoradiotherapy. These findings suggest that BST2 likely mediates platinum resistance in NPC, offering guidance for personalized and precise treatment strategies for patients with NPC.

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

“…The human NPC 5-8F and CNE2 cell lines were provided by the Research Center of Clinical Oncology of the Affiliated Jiangsu Cancer Hospital (Nanjing Medical University, Nanjing, China). Although it was reported that the CNE2 cell line was potentially contaminated on September 2014 (19), several studies based on this cell line have been published afterwards (20)(21)(22)(23), which seem to support the authors' view that the misidentification issue was unlikely to affect the outcomes of the present study.…”

Spatiotemporal homogeneity and distinctness of the T‐cell receptor β‐chain repertoires in Epstein–Barr virus‐associated primary and metastatic nasopharyngeal carcinomas

“…As expected, we also found the T‐cell clonotypes expanding secondary to other viral infections such as influenza‐A, cytomegalovirus, human immunodeficiency virus, hepatitis C virus and yellow fever virus in 58 patients (69%) (Supporting Information, Table S3). Moreover, 10 TCR beta clones responding to the known neoantigens of bone marrow stromal antigen 2 (BST2), melanoma antigen recognized by T cells 1 (MLANA) or transketolase (TKT) were identified in 20 patients (24%) (Table ) . However, most of the CDR3 sequences from the TILs of NPCs were not discovered in the public databases, suggesting our tumor‐shared clonotype dataset might likely include NPC‐exclusive clonality.…”

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling

“…Human nasopharyngeal cancer cell lines, CNE2 and HONE1 (Han et al, ; Kuang et al, ), were cultured in RPMI‐1640 Medium (Gibco, Carlsbad, CA, USA) contained 10% fetal bovine serum (Gibco, Carlsbad, CA, USA), 1% penicillin‐streptomycin (Gibco, Carlsbad, CA, USA), and maintained at 37°C in a humidified 5% CO 2 environment. Genistein was obtained from Sigma (St. Louis, MO, USA).…”