CTCF-induced upregulation of HOXA11-AS facilitates cell proliferation and migration by targeting miR-518b/ACTN4 axis in prostate cancer

Prostate. 2020 Apr;80(5):388-398. doi: 10.1002/pros.23953. Epub 2020 Jan 23.


Background: Testified as crucial participators in different types of human malignancies, long noncoding RNAs (lncRNAs) have been revealed to exert a significant effect on the complicated courses of tumor progression. Although existing literatures have revealed the oncogenic role of lncRNA homeobox A11 antisense RNA (HOXA11-AS) in multiple cancers, the underlying role of HOXA11-AS in prostate cancer (PCa) and its potential molecular mechanism remains poorly understood.

Aim: To decipher the molecular performance of HOXA11-AS in PCa.

Methods: The expression of HOXA11-AS, miR-518b and actinin alpha 4 (ACTN4) was detected by a real-time quantitative polymerase chain reaction. Colony formation, EdU, flow cytometry, wound healing, and transwell assays were utilized to explore the biological role of HOXA11-AS in PCa. The interaction between RNAs (CCCTC-binding factor [CTCF], HOXA11-AS, miR-518b, and ACTN4) was tested via chromatin immunoprecipitation, luciferase reporter and RNA immunoprecipitation assays.

Results: HOXA11-AS in PCa cells was expressed at high levels. Silenced HOXA11-AS in PCa cells could lead to a significant elevation in the abilities of cell proliferation and migration whereas a remarkable declination in cell apoptosis capability. Subsequent molecular mechanism assays confirmed that HOXA11-AS bound with miR-518b and negatively regulates miR-518b expression. Besides, HOXA11-AS could regulate the expression of ACTN4 by sponging miR-518b. Moreover, rescued-function assays revealed that miR-518b inhibition or ACTN4 upregulation reversed the repressive effect of HOXA11-AS knockdown on PCa progression. Furthermore, CTCF was validated to activate HOXA11-AS transcription in PCa cells.

Conclusions: CTCF-induced upregulation of HOXA11-AS facilitates PCa progression via miR-518b/ACTN4 axis, providing a new target for PCa treatment.

Keywords: ACTN4; CTCF; HOXA11-AS; PCa; miR-518b.

MeSH terms

  • Actinin / biosynthesis
  • Actinin / genetics*
  • Actinin / metabolism
  • Apoptosis / genetics
  • CCCTC-Binding Factor / biosynthesis
  • CCCTC-Binding Factor / genetics*
  • CCCTC-Binding Factor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Chromatin Immunoprecipitation
  • Gene Knockdown Techniques
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • PC-3 Cells
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Antisense / biosynthesis
  • RNA, Antisense / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transcription, Genetic
  • Transfection
  • Up-Regulation


  • ACTN4 protein, human
  • CCCTC-Binding Factor
  • CTCF protein, human
  • HOXA11 protein, human
  • Homeodomain Proteins
  • MIRN518 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Small Interfering
  • Actinin