Long noncoding RNA ADPGK-AS1 promotes cell proliferation, migration, and EMT process through regulating miR-3196/OTX1 axis in breast cancer

In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):522-532. doi: 10.1007/s11626-019-00372-1. Epub 2019 Jul 1.

Abstract

Emerging evidences exposed that long noncoding RNAs (lncRNAs) play important roles in various tumor progression including breast cancer (BC). However, the role of lncRNA ADP-dependent glucokinase antisense RNA 1 (ADPGK-AS1) in BC progression remains undiscovered. Hence, this study aimed to investigate the role of ADPGK-AS1 in BC. qRT-PCR was performed to investigate ADPGK-AS1 expression level in BC tissues and cell lines. The effect of ADPGK-AS1 knockdown on BC cellular process was assessed by loss-of-function assay. Luciferase reporter and RIP assay were performed to investigate the combination between ADPGK-AS1 and miR-3196. The combination between miR-3196 and orthodenticle homeobox 1 (OTX1) was verified by luciferase reporter assay. Finally, rescue assays were performed to confirm the effects of ADPGK-AS1/miR-3196/OTX1 axis on BC development. ADPGK-AS1 expression level was upregulated in BC tissues and cell lines. High expression of ADPGK-AS1 predicted poor prognosis for BC patients. Functionally, ADPGK-AS1 promoted cell proliferation, migration, induced epithelial-mesenchymal transition (EMT) process, and suppressed cell apoptosis. Mechanistically, ADPGK-AS1 acted as a miR-3196 sponge to release OTX1 in BC cells. Currently, ADPGK-AS1 acted as a competing endogenous RNA (ceRNA) via modulating miR-3196/OTX1 axis in BC.

Keywords: ADPGK-AS1; Breast cancer; OTX1; miR-3196.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Glucokinase / genetics*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Middle Aged
  • Otx Transcription Factors / genetics*
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics*

Substances

  • MicroRNAs
  • OTX1 protein, human
  • Otx Transcription Factors
  • RNA, Antisense
  • RNA, Long Noncoding
  • ADP-dependent glucokinase
  • Glucokinase