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

DNA Cell Biol. 2020 Jan;39(1):69-77. doi: 10.1089/dna.2019.5063. Epub 2019 Nov 8.

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 (UCA1) in multidrug resistance of retinoblastoma and its potential molecular mechanism. In this study, we observed that UCA1 was significantly upregulated in chemoresistant retinoblastoma tissues and multidrug resistant retinoblastoma cell lines and predicted an unfavorable overall survival. Functionally, knockdown of UCA1 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 UCA1 functioned as a miRNA sponge to increase stathmin 1 (STMN1) expression through sponging miR-513a-5p. In addition, silence of miR-513a-5p or STMN1 overexpression could partly reverse UCA1 knockdown-induced inhibitory effects on proliferation and multidrug resistance of retinoblastoma cells. Overall, this study is the first to demonstrate that UCA1 plays a critical role in retinoblastoma chemoresistance, and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of retinoblastoma.

Keywords: STMN1; UCA1; miR-513a-5p; multidrug resistance; retinoblastoma.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Carboplatin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Cisplatin / pharmacology
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / genetics*
  • Etoposide / pharmacology
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Retinoblastoma / drug therapy
  • Retinoblastoma / genetics*
  • Retinoblastoma / pathology
  • Vincristine / pharmacology

Substances

  • Antineoplastic Agents
  • MIRN513 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • Vincristine
  • Etoposide
  • Carboplatin
  • Cisplatin
  • Fluorouracil