Radioresistance has been one of the impediments to effective nasopharyngeal carcinoma (NPC) therapy in clinical settings. Epstein‐Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed in NPC and has potent effects on radioresistance. It has been detected in extracellular vesicles (EVs) or exosomes and shown to promote tumor proliferation and invasive potential. However, whether LMP1‐positive EVs can confer radioresistance to cancer cells and the mechanism used to promote radioresistance need to be elucidated. In this study, the data showed that EVs derived from LMP1‐positive NPC cells could induce recipient NPC cell proliferation and invasion and suppress apoptosis, especially promoting radioresistance. In addition, LMP1 could increase the secretion of LMP1‐positive EVs. Furthermore, transmitted LMP1 subsequently performed its oncogenic functions through activating P38 MAPK signaling in recipient cells, and inhibiting P38 activity could efficaciously restore the sensitivity of NPC cells to ionizing radiation (IR). Finally, we found that LMP1‐positive EVs could promote tumor growth and P38 inhibition eliminates this promoting effect in vivo, and EV formation is associated with a poor prognosis in NPC patients. These results showed that a few cells expressing LMP1 could enhance the radioresistance of NPC cells through potentially impacting the infected host and also modulating the tumor microenvironment.

Testicular germ cell tumors (TGCTs) are a diverse group of neoplasms that are derived from dysfunctional fetal germ cells and can also present in extragonadal sites. The genetic drivers underlying malignant transformation of TGCTs have not been fully elucidated so far. The aim of the present study is to clarify the functional role and regulatory mechanism of miR‐196a‐5p in TGCTs. We demonstrated that miR‐196a‐5p was downregulated in TGCTs. It can inhibit the proliferation, migration, and invasion of testicular tumor cell lines including NT‐2 and NCCIT through targeting the NR6A1 gene, which we proved its role in promotion of cell proliferation and repression of cellular junction and aggregation. Mechanistically, NR6A1 inhibited E‐cadherin through binding with DR0 sites in the CDH1 gene promoter and recruiting methyltransferases Dnmt1. Further, NR6A1 promoted neuronal marker protein MAP2 expression in RA‐induced neurodifferentiation of NT‐2 cells and testicular tumor xenografts. Clinical histopathologically, NR6A1 was positively correlated with MAP2, and negatively correlated with E‐cadherin in TGCTs. These findings revealed that the miR‐196a‐5p represses cell proliferation, migration, invasion, and tumor neurogenesis by inhibition of NR6A1/E‐cadherin signaling axis, which may be a potential target for diagnosis and therapy of TGCTs.

Glioma is a primary tumor derived from gliocyte, accounting for approximately 40% to 50% of intracranial brain tumors. Glioma is classified into I-IV grade based on different histopathological characteristics, among which grade IV glioma is the most malignant glioblastoma (GBM), representing the most common form of glioma in the adult population. 1 Because of the malignant proliferation, radiotherapy, and chemotherapy resistance and high recurrence rate of GBM, patients' median survival time is only 12-15 months. 2,3 Therefore, it is urgent to explore the molecular mechanism causing GBM to be more malignant than low-grade glioma (LGG).