Retinoblastoma (RB) is a common malignant tumor in children. Lidocaine is a local anesthetic and anti-arrhythmic drug, and has been reported to possess anti-tumor properties. MicroRNAs (miRs) are a group of endogenous small noncoding RNAs that have important roles in various biological processes via actions on target genes. The aim of the present study was to investigate the effect of lidocaine on retinoblastoma in vitro and in vivo . CCK-8 assay and flow cytometry assay were used to measure cell viability and apoptosis. The relationship between miR-520a-3p and EGFR was predicted and confirmed by TargetScan and dual-luciferase reporter assay. For in vivo study, tumor xenograft was performed. In addition, gene and protein expression was detected using reverse transcription-quantitative polymerase chain reaction and western blotting respectively. In the present study, it was observed that lidocaine inhibited the proliferation and induced the apoptosis of RB cells. miR-520a-3p was reported to be downregulated in RB tissues and cell lines; treatment with lidocaine increased the expression of miR-520a-3p in RB cells. The human epidermal growth factor receptor (EGFR) was identified as a direct target of miR-520a-3p, and its expression was negatively associated with that of miR-520a-3p. Additionally, EGFR was upregulated in RB tissues and cell lines; treatment with lidocaine decreased the expression of EGFR in RB cells. Furthermore, compared with treatment with lidocaine alone, the combination of transfection with miR-520a-3p inhibitor and lidocaine treatment significantly decreased the expression of miR-520a-3p, increased EGFR expression, promoted RB cell proliferation and reduced the apoptosis of cells in vitro , and increased tumor volume and weight in vivo . The results indicated that lidocaine reduced the proliferation and induced the apoptosis of RB cells by decreasing EGFR expression via the upregulation of miR-520a-3p, suggesting that the miR-520a-3p/EGFR axis may be a novel therapeutic target in the treatment of RB.

Purpose. The exact effects of histone deacetylase 3 (HDAC3) inhibition in DR related retinal ganglion cells (RGCs) death remained unclear. This study is aimed at detecting the influence of HDAC3 on the high-glucose-induced retinal ganglion cell death. Methods. The retinal HDAC3 expression in DR of different time points was analyzed by immunohistochemical assay and western blot. Besides, the expression of HDAC3 and both retinal thickness and RGC loss were analyzed. The effects of HDAC3 inhibitor on cell viability, oxidative stress, and apoptosis in high-glucose- (HG-) treated RGCs were analyzed. Both inflammatory and antioxidative factors were detected by ELISA. Results. Advanced effects of HDAC3 inhibition on the expression of NLRP3 inflammasome were detected using western blots. High HDAC3 expression was detected only in the late DR mice (4 months of diabetes duration) but not early DR mice (2 months of diabetes duration). The immunohistochemical assay showed that HDAC3 expression was correlated with both retinal thickness and RCG contents. HDAC3 inhibitor significantly protected the HG-treated RGCs from damaged cell viability, severe apoptosis, and oxidative stress. Advanced pathway analyses showed that HDAC3 inhibition inactivated NLRP3 inflammasome and thus alleviated retinal inflammation. Conclusion. In conclusion, HDAC3 was involved in RGC loss and thus promoted the progression of neurodegeneration of DR. Besides, HDAC3 inhibitor demonstrated protective effects in neurodegeneration in DR through downregulation of NLRP3 activity. The effects of HDAC3 inhibitor in DR management should be confirmed in clinical trials.