ABSTRACT. MicroRNAs (miRs) are associated with tumor progression in various cancers, such as gastric and hepatic carcinomas, and lung cancer. miR-301a is overexpressed and displays oncogenic activity in cancers. We investigated the biological involvement of miR301a in osteosarcoma (OS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze expression levels of miR-301a in 24 OS and matched adjacent non-tumor tissues. A miR-301a mimic was transferred into OS cell lines U-2 OS and MG-63 to upregulate miR-301a. The effects of miR-301a were investigated by examining cell proliferation, migration, and the cell cycle. The miR-301 target was predicted by TargetScan and confirmed by western blotting and qRT-PCR. The expression of miR-301a was significantly higher in OS tissues compared with the matched adjacent non-tumor tissues (0.959 ± 0.39 vs 3.9516 ± 1.18). Upregulated miR-301a significantly increased proliferation at 48 and 72 h compared to the negative control (U-2 OS: 2.11 ± 0.21 vs 2.88 ± 0.24; 2.70 ± 0.26 vs 3.71 ± 0.24; MG-63: 2.19 ± 0.20 vs 3.19 ± 0.22; 3.1 ± 0.25 vs 4.01 ± 0.27) and migration capability (U-2 OS: 100 ± 20.19 vs 150.68 ± 32.83; MG-63: 100 ± 17.20 vs 133.35 ± 26.26), and decreased apoptosis in both U-2 OS (10.87 ± 2.53 vs 4.01 ± 2.23) and MG-63 (15.26 ± 2.15 vs 8.25 ± 3.07). The cell cycle studies revealed that miR-301a caused an increase of the G2 population in U-2 OS (38.6 ± 6.58 vs 47.2 ± 7.27) and . Additional experiments indicated that CDC14A was upregulated by miR-301a (0.63 ± 0.06 vs 0.98 ± 0.06; 1.49 ± 0.25 vs 2.99 ± 0.14). Overexpressed miR-301a may increase CDC14A expression and promote cell proliferation and migration in OS cells. Therefore, miR301a may be useful for osteosarcoma diagnosis and therapy.
PURPOSE: To evaluate visual acuity (VA) outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DMO). METHODS: In this retrospective cohort study, electronic medical records for all patients undergoing intravitreal injections (IVI) in a tertiary referral centre between March 2013 and October 2018 were analysed. Treatment response in terms of visual acuity outcomes were reported for all eyes over a 4-year observation period. RESULTS: Our cohort includes 2616 DMO eyes of 1965 patients over 48 months. Cox proportional hazards modelling identified injection number (hazard ratio [HR] = 1.18), male gender (HR = 1.13), and baseline VA (HR = 1.09) as independent predictors to reach a favorable visual outcome of more than 70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Half of our cohort reached 70 letters 1.9 months after starting anti-VEGF therapy. Of those that reached 70 letters, 50% fell below 70 by 14.7 months. CONCLUSION: To date, this is the largest single center cohort study and over the longest observation period reporting on real-life outcomes of anti-VEGF in DMO. We have made an anonymised version of our dataset available on an open-source data repository as a resource for all clinical researchers globally.
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