Department of Ocular Fundus Disease, Cangzhou Eye Hospital, Cangzhou Central Hospital, Cangzhou, China.
DNA Cell Biol. 2020 Jan;39(1):69-77. doi: 10.1089/dna.2019.5063. Epub 2019 Nov 8.
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 () in multidrug resistance of retinoblastoma and its potential molecular mechanism. In this study, we observed that was significantly upregulated in chemoresistant retinoblastoma tissues and multidrug resistant retinoblastoma cell lines and predicted an unfavorable overall survival. Functionally, knockdown of 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 functioned as a miRNA sponge to increase stathmin 1 () expression through sponging miR-513a-5p. In addition, silence of miR-513a-5p or overexpression could partly reverse knockdown-induced inhibitory effects on proliferation and multidrug resistance of retinoblastoma cells. Overall, this study is the first to demonstrate that plays a critical role in retinoblastoma chemoresistance, and may serve as a potential diagnostic biomarker and therapeutic target of retinoblastoma.
化疗耐药性是癌症治疗的主要障碍之一。长链非编码 RNA（lncRNAs）的异常表达广泛参与多种癌症的化疗耐药性。本研究旨在探讨尿路上皮癌相关 1（）在视网膜母细胞瘤多药耐药中的作用及其潜在的分子机制。在本研究中，我们观察到在化疗耐药性视网膜母细胞瘤组织和多药耐药性视网膜母细胞瘤细胞系中显著上调，并预测总生存期不良。功能上，敲低显着抑制增殖，并使视网膜母细胞瘤细胞对多种化疗药物敏感，包括长春新碱（VCR）、卡铂（CBP）、顺铂（DDP）、VP-16（依托泊苷）和 5-氟尿嘧啶（5-Fu）。机制研究表明，通过海绵吸附 miR-513a-5p，作为 miRNA 海绵增加 stathmin 1（）的表达。此外，沉默 miR-513a-5p 或过表达 可以部分逆转 敲低诱导的对视网膜母细胞瘤细胞增殖和多药耐药性的抑制作用。总的来说，这项研究首次表明 在视网膜母细胞瘤化疗耐药性中发挥关键作用，并且 可能作为视网膜母细胞瘤的潜在诊断生物标志物和治疗靶点。
