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Highlights • High positive rate of EBV in NPC tissues. • miR-BART4 highly expressed in EBV positive NPC tissues. • Inhibition of miR-BART4 suppresses growth and invasion and induces apoptosis of NPC. • EBVmay inhibit its radiosensitivity by overexpression of miR-BART4. • Overexpression of miR-BART4 regulates biological characteristics of NPC cells by targeting PTEN. Abstract Objective This study aims to explore the role of Epstein-Barr virus (EBV) miR-BART4 in occurrence and progression of nasopharyngeal carcinoma (NPC) and its effect on radiosensitivity. Method The expressions of EBV and miR-BART4 in 108 cases of NPC tissues and 97 cases of chronic nasopharyngeal inflammation tissues were determined by real time quantitative polymerase chain reaction (PCR), and the relationship between the expression of miR-BART4 and the clinicopathological features of NPC was analyzed. Cell lines, HONEl, CNEl, CNE2, C666-1, 6-10B, and NP-69 were used to compare the expression of miR-BART4, in which the CNE2 cells were selected for further experiments. CNE2 cells were grouped into blank group, negative control (NC) group, miR-BART4 inhibitors group and miR-BART4 mimics group. Cells in above groups were under radiation of 6 Gy X ray for 12 h before grouped into control group, 6 Gy group, NC + 6 Gy group, miR-BART4 inhibitors + 6 Gy group and miR-BART4 mimics + 6 Gy group. Cell proliferation, clone formation ability, cell apoptosis, invasion and migration ability were measured by MTT assay, clone formation assay, flow cytometry (FCM), Transwell assay and scratch test, respectively. Western blot analysis was used to detect the expression of apoptosis-related proteins (cleaved caspase-3, Bax and Bcl-2) and epithelial-mesenchymal transition (EMT) marker protein E-cadherin and Vimentin. mRNA and protein expression of PTEN were detected by qRT-PCR and western blot. Bioinformatics software and luciferase activity experiments were used to verify the targeting relationship between miR-BART4 and PTEN. Results Positive rate of EBV in NPC tissues (93.5%) was remarkably higher than that in chronic nasopharyngeal inflammation tissues (21.6%). miR-BART4 was highly expressed and mRNA and protein expression of PTEN was lowly expressed in EBV positive NPC tissues compared with EBV negative NPC tissues and chronic nasopharyngeal inflammation tissues. The expression of miR-BART4 was related to the clinical stage, lymph node metastasis and differentiation degree of NPC. Expression of miR-BART4 in CNE2, CNEl, HONEl, C666-1, 6-10B, 5-8F cells was higher than that in NP-69 cells. In CNE2 and C666-1 cell experiments, compared with blank group and NC group, miR-BART4 inhibitors group had decreased miR-BART4 expression, increased mRNA and protein expression of PTEN, cell survival rate, invasion and migration ability and increased cell apoptosis rate, which is totally contrary to the observation in miR-BART4 mimics group. The radiosensitive NPC tissues had higher miR-BART4 expression than that in radio-resistance NPC tissues. In comparison to 6 Gy group and NC + 6 Gy group, cell survival rate and clone number was inhibited, but the cell apoptosis rate was increased in miR-BART4 inhibitors +6 G group, in contrary to the observation in miR-BART4 inhibitors + 6 Gy group. Bioinformatics software and luciferase activity experiments confirmed that miR-BART4 could inhibit the expression of PTEN. Conclusion EBV may promote development and progression of NPC by up-regulating miR-BART4 expressions, consequently inhibiting its radiosensitivity, whose effect may be related to the targeting inhibition of PTEN expression. [ABSTRACT FROM AUTHOR]

• Effect of miR-483−3p on RA FLSs proliferation, apoptosis, & cell cycle was studied. • miR-483−3p levels were increased in synovium and FLSs of patients with RA. • Up-regulated miR-483−3p promoted proliferation and suppressed apoptosis. • Insulin-like growth factor 1 was verified as a direct target gene of miR-483−3p. • Our findings might provide a potential therapeutic target for RA. Accumulating evidence suggests that miR-483−3p is implicated in maintaining biological properties in human cancers. However, its biological roles in rheumatoid arthritis (RA) remain unknown. miR-483−3p levels in synovial tissue samples and fibroblast-like synoviocytes (FLSs) were determined using quantitative real-time PCR. The CCK-8 assay and EdU staining were performed to assess cell proliferation in RA FLSs after transfection with miR-483−3p mimics or inhibitor. Flow cytometry with Annexin V-FITC staining or PI staining was performed to assess apoptosis or cell cycle progression in RA FLSs, respectively. miR-483−3p was upregulated in RA, which markedly promoted cell proliferation, induced the G0/G1-to-S phase transition, and suppressed apoptosis in RA FLSs, whereas miR-483−3p silencing yielded opposite results. Moreover, insulin growth factor 1 (IGF-1) was detected as a direct miR-483−3p target. IGF-1 silencing partially restored cell proliferation, the G0/G1-to-S phase transition, and apoptosis suppression in RA FLSs via miR-483−3p inhibition. Our results showed that miR-483−3p promotes RA FLSs proliferation by targeting IGF-1, suggesting a potential strategy for diagnostic and treatment strategy for RA. [ABSTRACT FROM AUTHOR]

• Effect of miR-410-3p on RA FLS proliferation, apoptosis, & cell cycle was studied. • miR-410-3p levels were reduced in synovium and FLSs of patients with RA. • Up-regulated miR-410-3p inhibited proliferation and induced apoptosis. • Yin Yang 1 transcription factor was verified as a direct target gene of miR-410-3p. • Our findings might provide a potential therapeutic target for RA. In our previous study, miR-410-3p had been confirmed to regulate inflammatory cytokine release in rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). However, other biological functions of miR-410-3p in RA FLSs still remain unexplored. In the present study, we focused on the effect of miR-410-3p on proliferation, apoptosis, and cell cycle of RA FLSs, and explored the potential underlying mechanism. miR-410-3p mRNA levels in the synovium and FLSs of patients with RA and of healthy controls were quantitated by RT-qPCR. The levels of miR-410-3p were reduced in both synovium and FLSs from patients with RA. Next, we focused on the roles of miR-410-3p in cell viability, apoptosis, and cell cycle, by transfecting miR-410-3p mimics and inhibitor into RA FLSs, and conducting CCK-8 assay, EdU staining and flow cytometry. Results showed that miR-410-3p up-regulation suppressed proliferation, promoted apoptosis and G1-S phase transition while miR-410-3p down-regulation had opposite effects. YY1 was verified as a direct target gene of miR-410-3p through the luciferase reporter system; YY1 up-regulation was able to rescue the effects of miR-410-3p in RA FLSs. Taken together, our current findings might provide a potential therapeutic target for RA. [ABSTRACT FROM AUTHOR]