EBV-miR-BART12 accelerates cancer cell migration and invasion through targeting TPPP1 in EBV associated cancer

Background: Epstein-Barr virus (EBV) is suggested to actively utilize its EBV microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. But its role in tumor development and maintenance remains unclear. The objective of this study is to examine EBV-miRNA-BART12 implicated in EBV associated carcinogenesis. Methods :Expression of EBV-miRNA-BART12 and TPPP1 (Tubulin Polymerization Promoting Protein 1) was confirmed by GEO datasets, RT-PCR and in situ hybridization. Luciferase analyses, RT-PCR and western blotting experiments examined and confirmed that EBV-miRNA-BART12 targeted the 3'-UTR of TPPP1 mRNA. Migration and invasion ability were measured by wound healing and transwell assay. And the mechanism was assessed by western blotting and immunofluorescence. Results : Our results showed that EBV-miRNA-BART12 was highly expressed and TPPP1 was lowly expressed in NPC and/or GC and tightly associated with these patients' prognosis. Additionally, EBV-miR-BART12 advanced the HDAC6 (Histone Deacetylase 6) activity in cells by inhibiting TPPP1, and stimulated acetylation of α-tubulin and β-catenin, thereby increasing the microtubule instability and activating the epithelial-mesenchymal transition (EMT) process. Conclusion : EBV-encoded BART12 promotes migration and invasion of EBV associated NPC and gastric cancer by inhibiting TPPP1 mRNA and promoting the microtubule instability and the cellular EMT process.