Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.

Background Cisplatin (DDP) resistance in ovarian cancer (OC) patients usually leads to treatment failure and increased mortality. Anlotinib has been shown to improve progression-free survival and overall survival in patients with platinum-resistant ovarian cancer, but the mechanism is unclear. This study aims to explore the mechanism by which anlotinib ameliorates platinum resistance in OC cells. Methods Cell viability was detected by the 3-4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) method, and the apoptosis rate and changes in the cell cycle distribution were evaluated by flow cytometry. Bioinformatics analysis was used to predict the potential gene target of anlotinib in DDP-resistance SKOV3 cells, and its expression was verifies it by RT-qPCR, western blotting and immunofluorescence staining. Finally, ovarian cancer cells overexpressing AURKA were constructed, and the predicted results were verified by animal experiments. Results Anlotinib effectively induced apoptosis and G2/M arrest in OC cells and decreased the proportion of EdU-positive cells. AURKA was identified as a possible key target of anlotinib for inhibiting tumorigenic behaviors in SKOV3/DDP cells. Through combined immunofluorescence and western blot analyses, it was demonstrated that anlotinib could effectively inhibit the protein expression of AURKA and upregulate the expression of p53/p21, CDK1, and Bax protein. After overexpression of AURKA in OC cells, the induction of apoptosis and G2/M arrest by anlotinib were significantly inhibited. Anlotinib also effectively inhibited the growth of tumors in nude mice injected with OC cells. Conclusions This study demonstrated that anlotinib can induce apoptosis and G2/M arrest in cisplatin-resistant ovarian cancer cells through the AURKA/p53 pathway.