Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reported that one of the key miRNAs encoded by EBV, EBV-miR-Bart1-5P, can significantly promote nasopharyngeal carcinoma (NPC) cell glycolysis and induces angiogenesis in vitro and in vivo. Mechanistically, EBV-miR-Bart1-5P directly targets the α1 catalytic subunit of AMP-activated protein kinase (AMPKα1) and consequently regulates the AMPK/mTOR/HIF1 pathway which impelled NPC cell anomalous aerobic glycolysis and angiogenesis, ultimately leads to uncontrolled growth of NPC. Our findings provide new insights into metabolism and angiogenesis of NPC and new opportunities for the development of targeted NPC therapy in the future.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors.

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Background: Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. Methods: CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. Results: The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. Conclusions: We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.

Background Identification of less costly and accurate methods for monitoring novel coronavirus disease 2019 (CoViD-19) transmission has attracted much interest in recent times. Here, we evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Guangzhou, China. Methods We evaluated 8097 throat swap samples collected from individuals who came for a health check-up or fever clinic in The Third Affiliated Hospital, Southern Medical University between March 4, 2020 and April 26, 2020. Samples were screened for CoViD-19 infection using the WHO-approved quantitative reverse transcription PCR (RT-qPCR) primers. The positive samples were classified into two groups (high or low) based on viral load in accordance with the CT value of COVID-19 RT-qPCR results. Each positive RNA samples were mixed with COVID-19 negative RNA or ddH2O to form RNA pools. Findings Samples with high viral load could be detected in pool negative samples (up to 1/1000 dilution fold). In contrast, the detection of RNA sample from positive patients with low viral load in a pool was difficult and not repeatable. Interpretation Our results show that the COVID-19 viral load significantly influences in pooling efficacy. COVID-19 has distinct viral load profile which depends on the timeline of infection. Thus, application of pooling for infection surveillance may lead to false negatives and hamper infection control efforts. Funding National Natural Science Foundation of China; Hong Kong Scholars Program, Natural Science Foundation of Guangdong Province; Science and Technology Program of Guangzhou, China.