Wang Nanye, Fan Huimin, Fu Shuhua, Li Shaojun, Zhou Bin, Jin Qifang, You Zhipeng
Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University Nanchang 330006, Jiangxi, China.
Department of Orthopedics, The Second Affiliated Hospital of Nanchang University Nanchang 330006, Jiangxi, China.
Am J Cancer Res. 2022 May 15;12(5):2160-2172. eCollection 2022.
Chemoresistance has become a major obstacle to effective retinoblastoma treatment. The urothelial cancer-associated gene 1 () is commonly considered an oncogene in certain types of cancer and is related to drug resistance. Nonetheless, the molecular mechanism and effect of in carboplatin resistance in retinoblastoma are unclear. In this study, expression was determined by sequential screening and lncRNA profile analysis, which is highly abundant in carboplatin-resistant retinoblastoma cells. Functional analyses revealed that promoted carboplatin resistance by promoting c-Met and AXL expression. Mechanistic studies revealed that facilitated c-Met and AXL expression as a ceRNA of miR-206. Importantly, retinoblastoma nude mouse model experiments revealed that targeting or c-Met and AXL can restore drug sensitivity in carboplatin-resistant retinoblastoma. Collectively, we found that is a mediator of carboplatin resistance in retinoblastoma cells. It competes with others as the endogenous RNA of miR-206, thus upregulating its targets, c-MET and AXL expression.
化疗耐药已成为视网膜母细胞瘤有效治疗的主要障碍。尿路上皮癌相关基因1（）在某些类型的癌症中通常被认为是一种癌基因，并且与耐药性有关。然而，其在视网膜母细胞瘤顺铂耐药中的分子机制和作用尚不清楚。在本研究中，通过序列筛选和lncRNA谱分析确定了的表达，其在顺铂耐药的视网膜母细胞瘤细胞中高度丰富。功能分析表明，通过促进c-Met和AXL表达来促进顺铂耐药。机制研究表明，作为miR-206的ceRNA促进了c-Met和AXL表达。重要的是，视网膜母细胞瘤裸鼠模型实验表明，靶向或c-Met和AXL可以恢复顺铂耐药的视网膜母细胞瘤的药物敏感性。总体而言，我们发现是视网膜母细胞瘤细胞中顺铂耐药的介质。它作为miR-206的内源性RNA与其他物质竞争，从而上调其靶标c-MET和AXL的表达。
