UCA1 confers paclitaxel resistance to ovarian cancer through miR-129/ABCB1 axis

Biochem Biophys Res Commun. 2018 Jul 2;501(4):1034-1040. doi: 10.1016/j.bbrc.2018.05.104. Epub 2018 May 19.

Abstract

Increasing evidence has demonstrated the involvement of dysregulated long non-coding RNAs (lncRNAs) in chemoresistance acting as potential oncogenes or tumor suppressors in various cancers. Nevertheless, the profound molecular mechanisms of lncRNAs in ovarian cancer (OC) chemoresistance is not well elucidated. The objective of this work was to investigate the role and molecular mechanisms of urothelial carcinoma associated 1 (UCA1) in paclitaxel (PTX) resistance in OC. Our results indicated that UCA1 was significantly up-regulated in PTX-resistant OC cells (SKOV3/PTX and HeyA-8/PTX) compared with their parental cells (SKOV3 and HeyA-8). Functionally, UCA1 knockdown sensitized SKOV3/PTX and HeyA-8/PTX cells to PTX through enhancing PTX-induced apoptosis. Mechanistically, UCA1 silencing induced PTX sensitivity of SKOV3/PTX and HeyA-8/PTX cells by de-repressing ABCB1 through sponging miR-129. Collectively, our study elaborated a novel UCA1/miR-129/ABCB1 regulatory axis underlying PTX resistance of OC cells, providing a potential therapeutic target for OC.

Keywords: ABCB1; Ovarian cancer; Paclitaxel resistance; UCA1; miR-129.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use*
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • MicroRNAs
  • Mirn129 microRNA, human
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • Paclitaxel