Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-α expression

Prostate. 2021 Apr;81(5):271-278. doi: 10.1002/pros.24102. Epub 2021 Feb 8.

Abstract

Background: A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC).

Methods: The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway.

Results: The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression.

Conclusion: Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.

Keywords: TGF-α; cell invasion; circANKS1B; miR-152-3p; prostate cancer.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Gene Expression / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness / genetics
  • PC-3 Cells
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • RNA, Circular / genetics
  • RNA, Circular / physiology*
  • Transforming Growth Factor alpha / genetics*
  • Up-Regulation / genetics

Substances

  • ANKS1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN152 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • TGFA protein, human
  • Transforming Growth Factor alpha