lncRNA <i>UCA1</i> Increases Proliferation and Multidrug Resistance of Retinoblastoma Cells Through Downregulating miR-513a-5p

Abstract

Chemoresistance is one of the major obstacles for cancer therapy. Abnormal expression of long noncoding RNAs (lncRNAs) was broadly implicated in chemoresistance of multiple cancers. This study was aimed to investigate the function of urothelial cancer associated 1 (<i>UCA1</i>) in multidrug resistance of retinoblastoma and its potential molecular mechanism. In this study, we observed that <i>UCA1</i> was significantly upregulated in chemoresistant retinoblastoma tissues and multidrug resistant retinoblastoma cell lines and predicted an unfavorable overall survival. Functionally, knockdown of <i>UCA1</i> remarkably inhibited proliferation and sensitized retinoblastoma cells to multiple chemotherapy drugs, including vincristine (VCR), carboplatin (CBP), cisplatin (DDP), VP-16 (etoposide), and 5-fluorouracil (5-Fu). Mechanistic studies demonstrated that <i>UCA1</i> functioned as a miRNA sponge to increase stathmin 1 (<i>STMN1</i>) expression through sponging miR-513a-5p. In addition, silence of miR-513a-5p or <i>STMN1</i> overexpression could partly reverse <i>UCA1</i> knockdown-induced inhibitory effects on proliferation and multidrug resistance of retinoblastoma cells. Overall, this study is the first to demonstrate that <i>UCA1</i> plays a critical role in retinoblastoma chemoresistance, and <i>UCA1</i> may serve as a potential diagnostic biomarker and therapeutic target of retinoblastoma.