卡铂耐药是视网膜母细胞瘤(RB)治疗失败的主要原因，但机制不祥。研究报道细胞自噬在卡铂耐药中发挥关键作用。预实验发现：circ-HIPK2是卡铂耐药RB细胞中增加最为显著的circRNA；降低circ-HIPK2的表达抑制RB耐药细胞自噬，并增强RB细胞对卡铂的敏感性；下调circ-HIPK2可抑制耐药细胞中自噬相关基因EZH2的表达，且RB组织中circ-HIPK2与EZH2的表达呈正相关。据此我们推测：circ-HIPK2通过调控EZH2增强细胞自噬，从而促进RB卡铂耐药。本项目拟先利用体内外实验研究circ-HIPK2在RB卡铂耐药中的作用，再阐明circ-HIPK2调控细胞自噬的分子机制；然后明确circ-HIPK2调控EZH2促进细胞自噬介导RB卡铂耐药的机制，最后分析RB组织中circ-HIPK2及EZH2的表达与患者临床病理特征的关系。本研究将为逆转RB卡铂耐药提供理论依据。

Carboplatin resistance is the main cause of treatment failure of retinoblastoma (RB), but its mechanism is still unclear. It has been reported that autophagy plays a key role in carboplatin resistance. Our preliminary experimental results show that circ-HIPK2 is the most highly expressed circRNAs in carboplatin-resistant RB cells. In addition, downregulation of circ-HIPK2 can inhibit autophagy in carboplatin-resistant RB cells, and enhance RB cell’s sensitivity to carboplatin. Further, our results also indicate that suppression of circ-HIPK2 level was associated with reduced the autophagy-related gene EZH2 level in carboplatin-resistant RB, and circ-HIPK2 level was positively correlated with EZH2 level in RB tissues. Based on this, we speculate that circ-HIPK2 promotes RB carboplatin resistance by regulating EZH2 to enhance cell autophagy. To test this hypothesis, we initially performed in vitro and in vivo experiments to determine the role of circ-HIPK2 in promoting carboplatin resistance in RB, to elucidate the mechanism of circ-HIPK2 in regulating autophagy of RB cells. Then, we will clarify the mechanism through which circ-HIPK2 mediates carboplatin resistance in RB by regulating EZH2 to enhance autophagy. Finally, we analyzed the correlation between the expression of circ-HIPK2 and EZH2, and the clinicopathological characteristics in RB.This study will provide a new theoretical basis for reversing resistance to carboplatin in the molecular targeted therapy of RB.