Senile cataract is a common age-related disease in ophthalmology. Hsa_circ_0004058 has been reported to be down-regulated in the lens epithelial cells of senile cataract patients, suggesting that hsa_circ_0004058 is associated with senile cataract. However, the underlying mechanism is still unknown. This study attempted to determine the functional role of hsa_circ_0004058 in senile cataract. We treated human lens epithelial cells (SRA01/04) with H₂O₂ as senile cataract model, and found that cell viability and autophagy of SRA01/04 cells were severely decreased by H₂O₂ treatment. Hsa_circ_0004058 was notably down-regulated in H₂O₂-treated SRA01/04 cells. Moreover, hsa_circ_0004058 overexpression reduced apoptotic cells and the expression of Cleaved-caspase-3 and Bax, and enhanced Bcl-2 expression in H₂O₂-treated SRA01/04 cells. However, hsa_circ_0004058 silencing caused the opposite results. Hsa_circ_0004058 up-regulation accelerated the expression of autophagy-related proteins LC3-II/LC3-I and Beclin-1 in H₂O₂-treated SRA01/04 cells, which was partly abolished by 3-Methyladenine (autophagy inhibitor). Additionally, hsa_circ_0004058 functioned as a competing endogenous RNA to competitive binding miR-186, and thus accelerated the expression of its down-stream target, ATG7. Hsa_circ_0004058 promoted autophagy of SRA01/04 cells by regulating miR-186/ATG7 axis. In conclusion, these data demonstrates that hsa_circ_0004058 inhibits apoptosis of SRA01/04 cells by promoting autophagy, which attributes to regulate miR-186/ATG7 axis. Thus, hsa_circ_0004058 may be a potential target for senile cataract treatment.

老年性白内障是眼科常见的年龄相关性疾病。据报道，hsa_circ_0004058 在老年性白内障患者的晶状体上皮细胞中表达下调，提示 hsa_circ_0004058 与老年性白内障相关。然而，其根本机制仍不清楚。本研究试图确定 hsa_circ_0004058 在老年性白内障中的功能作用。我们用H ₂ O ₂处理人晶状体上皮细胞(SRA01/04)作为老年性白内障模型，发现H ₂ O ₂处理后SRA01/04细胞的细胞活力和自噬严重降低。 Hsa_circ_0004058 在H ₂ O ₂处理的SRA01/04细胞中显着下调。此外，hsa_circ_0004058过表达减少了H ₂ O ₂处理的SRA01/04细胞中的凋亡细胞以及Cleaved-caspase-3和Bax的表达，并增强了Bcl-2的表达。然而，hsa_circ_0004058 沉默却导致了相反的结果。 Hsa_circ_0004058上调加速了H ₂ O ₂处理的SRA01/04细胞中自噬相关蛋白LC3-II/LC3-I和Beclin-1的表达，该表达被3-甲基腺嘌呤（自噬抑制剂）部分消除。此外，hsa_circ_0004058充当竞争性结合miR-186的竞争性内源RNA，从而加速其下游靶标ATG7的表达。 Hsa_circ_0004058通过调节miR-186/ATG7轴促进SRA01/04细胞的自噬。总之，这些数据表明 hsa_circ_0004058 通过促进自噬抑制 SRA01/04 细胞凋亡，这归因于调节 miR-186/ATG7 轴。 因此，hsa_circ_0004058可能是老年性白内障治疗的潜在靶点。