Background: Epstein-Barr virus (EBV)-produced non-coding RNAs, including circular RNA (circRNA), regulate host cell gene expression and play important roles in development of nasopharyngeal carcinoma (NPC). EBV-encoded circRNA circRPMS1 consists of the head-to-tail splicing of exons 2-4 from the RPMS1 gene. Its roles and mechanism on NPC remain unknown. Purpose: In this study, we investigated the biological functions and molecular mechanisms of circRPMS1 in tumor proliferation, apoptosis, invasion, metastasis and as a potential biomarker for NPC diagnosis and prognosis. Patients and methods: NPC tissues and the adjacent tissues were collected. Cell proliferation assay, cell apoptosis assay, cell invasion assay, luciferase reporter assay, RNA immunoprecipitation and tumor xenograft in nude mice were performed to analyze the circRPMS1 functions. Results: We found that EBV-encoded circRPMS1 was increased in metastatic NPC and was associated with short survival time. Knockdown of circRPMS1 inhibited cell proliferation, induced apoptosis and repressed cell invasion in EBV-positive NPC cells. Further mechanism investigation revealed that circRPMS1-meadiated NPC oncogenesis through sponging multiple miRNA and promoting epithelial-mesenchymal transition (EMT). The inhibitors of miR-203, miR-31 and miR-451 could reverse the effects of circRPMS1 knockdown on NPC cells. Conclusion: The findings indicate circRPMS1 as a potential therapeutic target for EBVassociated NPC. Our findings provide important understanding for the further elucidation on the therapeutic use of circRNA in NPC.

Despite significant medical advancement, nasopharyngeal carcinoma (NPC) remains one of the most difficult types of cancer to detect and treat. Circular RNA (circRNA) signatures may be used as prognostic and predictive factors for cancer. Previous studies indicated that the biological role of circular homeodomain interacting protein kinase 3 (HIPK3) has cancer type-specificity. The HIPK3 gene locus formats three circRNA isoforms: circRNA_100783, circRNA_0000285 and circRNA_100782. However, their roles in NPC remain unknown. In the present study, whether these circRNAs could be used as a biomarker for NPC diagnosis and predicting treatment response was investigated. Reverse transcription-quantitative polymerase chain reaction was performed to measure the levels of circRNA_100783, circRNA_0000285 and circRNA_100782 in NPC and adjacent tissues. In addition, the circRNA_0000285 levels were further confirmed in serum samples from patients with NPC and healthy controls. The results demonstrated that circRNA_0000285, but not circRNA_100782 and circRNA_100783, was significantly increased in NPC tissues and serum samples from patients with NPC, compared with adjacent tissues and serum samples from healthy controls, respectively. Furthermore, circRNA_0000285 expression was increased in patients with radioresistant NPC, compared with patients with radiosensitive NPC. Further analysis demonstrated that circRNA_0000285 was significantly associated with tumor size (P<0.001), differentiation (P=0.022), lymph node metastasis (P=0.035), distant metastasis (P=0.022) and Tumor-Node-Metastasis stage (P<0.001). Additionally, univariate and multivariate analyses indicated that circRNA_0000285 may be an independent prognostic factor for the outcome of patients with NPC. The present data indicated that circRNA_0000285 may be a novel biomarker for NPC and is involved in NPC radiosensitivity.

Background: Nasopharyngeal carcinoma (NPC) is one of the most difficult cancers to be detected and treated. Hunting for novel cancer-specific biomarkers for NPC patients is helpful for timely diagnosis and clinical treatment of NPC. Methods: In this study, high-throughput circRNA sequencing was used to screen the circRNAs with expression variation in NPC patients. qRT-PCR was used to detect the expression level of hsa_circRNA_001387 in the cancer tissues from 100 surgical patients, the peripheral blood samples from 100 radiotherapy patients and NPC cell lines. Based on clinical data of the patients, the relationship between hsa_circRNA_001387 and radiotherapy as well as antibody to Epstein-Barr (EB) virus was investigated. The use of this circRNA as a biomarker for NPC was also discussed. Results: Expression of hsa_circRNA_001387 was significantly increased in the tumor tissues of NPC surgical patients, in the peripheral blood samples of NPC radiotherapy patients and in the NPC cell lines (P<0.01). Expression of hsa_circRNA_001387 was significantly elevated in patients with well-differentiated tumors, lymph node metastasis and distant metastases, stage III-IV, positive EB virus, or family history of NPC. hsa_circRNA_001387 was closely associated with the prognosis of the patients. The overall survival and progression-free survival were shorter in patients with high expression. Through univariate and multivariate analyses, it was found that hsa_circRNA_001387 was considered as an independent factor for the prognosis of NPC patients. Conclusion: This study reported for the first time that expression of hsa_circRNA_001387 is significantly upregulated, and it was also indicated that hsa_circRNA_001387 can be used as a novel biomarker for NPC.

BackgroundAdvanced recurrent nasopharyngeal carcinoma (NPC) is a relatively common nasopharyngeal skull base disease for which there is no uniform treatment modality. Not all patients are satisfied with the efficacy of immunotherapy with or without chemotherapy.MethodsThis study included patients who underwent salvage endoscopic skull base nasopharyngectomy after immunotherapy between February 2017 and June 2021. Patient survival information was analyzed. Relevant publications were retrieved from five databases from December 1, 2011 to December 1, 2021. The outcomes of patients with advanced recurrent NPC who received programmed death 1 (PD-1) immunotherapy were collected and analyzed.ResultsNine patients who underwent skull base surgery, all of whom had previously undergone PD-1 immunotherapy, were included in this study. The 2-year overall survival (OS) and progression-free survival (PFS) rates of these patients were 25% and 29.2%, respectively. Eight publications involving 688 patients with advanced recurrent NPC were also included in this study. The combined complete response (CR), partial response (PR), and stable disease (SD) values were 2%, 23%, and 29%, respectively. The combined DCR included the three disease conditions, CR, PR, and SD, with a value of 53%. PD-1 monotherapy was more effective than PD-1 combination chemotherapy.ConclusionsPD-1 immunotherapy may improve the remission rate in patients with recurrent NPC. Salvage endoscopic skull base nasopharyngectomy may be another option for patients with poor immunotherapeutic outcomes. For patients with advanced recurrent NPC, better evidence-based medical data are needed to determine whether they should receive immunotherapy before or after surgery.

Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.