Chemoresistance has become a major obstacle to effective retinoblastoma treatment. The urothelial cancer-associated gene 1 (UCA1) is commonly considered an oncogene in certain types of cancer and is related to drug resistance. Nonetheless, the molecular mechanism and effect of UCA1 in carboplatin resistance in retinoblastoma are unclear. In this study, UCA1 expression was determined by sequential screening and lncRNA profile analysis, which is highly abundant in carboplatin-resistant retinoblastoma cells. Functional analyses revealed that UCA1 promoted carboplatin resistance by promoting c-Met and AXL expression. Mechanistic studies revealed that UCA1 facilitated c-Met and AXL expression as a ceRNA of miR-206. Importantly, retinoblastoma nude mouse model experiments revealed that targeting UCA1 or c-Met and AXL can restore drug sensitivity in carboplatin-resistant retinoblastoma. Collectively, we found that UCA1 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.
Keywords: AXL/c-Met; Retinoblastoma; UCA1; carboplatin resistance; miR-206.
AJCR Copyright © 2022.