Benefiting from more precise imaging and radiotherapy, patients with locoregionally nasopharyngeal carcinoma (NPC) have a significantly higher survival rate. Nonetheless, distant metastasis is still the predominant mode of failure. Advances in cancer research have highlighted that pathological angiogenesis is necessary for tumor metastasis by offering oxygen, nutrients, or cell metastatic conduits. MicroRNAs (miRNAs), a class of small noncoding RNAs, are increasingly implicated in modulation of angiogenesis in physiological and pathological conditions. Currently, we detected that miR-23a was highly enriched in NPC tissues at the metastatic or premetastatic stage, and its levels in NPC were associated with microvessel density. Subsequently, we proved that alteration of miR-23a expression modulated the growth, migration, and tube formation of HUVECs in vitro and affected the blood vessel outgrowth in the zebrafish model. Considering the possibility that extracellular miR-23a was horizontally transferred from CNE2 cells to HUVECs, we analyzed miR-23a encapsulated in exosomes, showing that overexpression of exosomal miR-23a in NPC promoted angiogenesis both in vitro and in vivo. Moreover, we provided evidences that miR-23a regulated angiogenesis by directly targeting testis-specific gene antigen (TSGA10). Taken together, our findings revealed that metastasis-associated miR-23a from NPC-derived exosomes plays an important role in mediating angiogenesis by targeting TSGA10.

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies of the head and neck. It arises from the nasopharynx epithelium and is associated with high morbidity and mortality. Long non‐coding RNA (lncRNA) have been reported to regulate gene interaction and play critical roles in carcinogenesis and progression. LncRNA‐ROR, a recently identified lncRNA, has been shown to be involved in initiation, progression and metastasis of several tumors, including hepatocellular carcinoma, breast cancer and glioma. However, whether lncRNA‐ROR is associated with the progression of NPC remains unknown. Resistance to radiotherapy and chemotherapy is the primary cause of NPC patients’ death. In this study, we found that lncRNA‐ROR was significantly upregulated in NPC tissues compared with normal tissues. Next, our study proved that lncRNA‐ROR was highly associated with the proliferation, metastasis and apoptosis of NPC. The enrichment of lncRNA‐ROR played a critucal functional role in chemoresistance. The mechanism by which NPC resists chemotherapy might be that lncRNA‐ROR suppress p53 signal pathway. Taken together, these data suggested that lncRNA‐ROR played an important role in the progression of NPC; thereby it might become a therapeutic target and reduce chemoresistance for NPC.

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Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

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Exosomes are nano-vesicles secreted by tumor cells. Exosomes can transfer complex biological information and induce a diverse signaling response in a wide array of pathological conditions, such as hypoxia. Hypoxia is associated with aggressive phenotypes and poor outcomes in nasopharyngeal carcinoma (NPC) patients. Here, we analyzed the role of exosomes from hypoxic NPC cells in enhancing the metastases of normoxic cells in a hypoxia-induced factor-1α (HIF-1α)-dependent manner. HIF-1α rapidly accumulates and trans-activates hundreds of genes, such as matrix metalloproteinases (MMPs). We found that MMP-13 was over-expressed in exosomes and cells under hypoxic conditions. HIF-1α depletion in hypoxic CNE2 cells led to decreased MMP-13 levels in exosomes and significantly reduced cell migration and invasion. Moreover, exosomal MMP-13 significantly up-regulated Vimentin expression while decreasing E-cadherin levels in CNE2 cells in vitro and in vivo. Furthermore, MMP-13 levels were closely associated with HIF-1α expression (r = 0.679, P < 0.001), lymph node metastasis, clinical stage (all P < 0.05) and poor prognosis in NPC patients (P < 0.01). In conclusion, our findings suggest that the hypoxic exosomes were loaded with MMP-13, which could enhance migration and invasiveness and induce microenvironment changes to promote NPC aggressiveness.

Taken together, these results indicate that miR-10 regulates the angiogenic behaviour in a Notch-dependent manner by directly targeting mib1.

Dysregulated microRNAs (miRNAs) are involved in carcinoma progression, metastasis, and poor prognosis. We demonstrated that in nasopharyngeal carcinoma (NPC), transactivated MIR106A-5p promotes a malignant phenotype by functioning as a macroautophagy/autophagy suppressor by targeting BTG3 (BTG anti-proliferation factor 3) and activating autophagy-regulating MAPK signaling. MIR106A-5p expression was markedly increased in NPC cases based on quantitative real-time PCR, miRNA microarray, and TCGA database analysis findings. Moreover, MIR106A-5p was correlated with advanced stage, recurrence, and poor clinical outcomes in NPC patients. In addition to three-dimensional cell culture assays, zebrafish and BALB/c mouse tumor models revealed that overexpressed MIR106A-5p targeted BTG3 and accelerated the NPC malignant phenotype by inhibiting autophagy. BTG3 promoted autophagy, and its expression was correlated with poor prognosis in NPC. Attenuation of autophagy, mediated by the MIR106A-5p-BTG3 axis, occurred because of MAPK pathway activation. MIR106A-5p overexpression in NPC was due to increased transactivation by EGR1 and SOX9. Our findings may lead to novel insights into the pathogenesis of NPC.