Circular RNA circHIPK3 modulates prostate cancer progression via targeting miR-448/MTDH signaling

Clin Transl Oncol. 2021 Dec;23(12):2497-2506. doi: 10.1007/s12094-021-02650-5. Epub 2021 Jun 17.

Abstract

Purpose: Prostate cancer (PCa) is one of the most diagnosed cancers in men worldwide. Several studies have identified that circular RNAs (circRNAs) have a crucial impact on the biological processes in PCa. Therefore, it is necessary to study the molecular mechanism of circRNAs in tumor progression and metastasis.

Methods: RNA interference was used to decrease circHIPK3 and MTDH expression. Overexpression vector was used to increase circHIPK3 and MTDH expression. Luciferase reporter assay were used to detect the relationship between circHIPK3 and miR-448 or between miR-448 and MTDH. MTT assay, colony formation assay and transwell assay were used to measure proliferation and migration of PCa cells.

Results: Circular RNA circHIPK3 was significantly increased in PCa tissues and cell lines. And overexpression of circHIPK3 promoted the migration, proliferation, and invasion of PC-3 and 22Rv1 cells, while knockdown of circHIPK3 markedly repressed the above-mentioned series of biological processes. Furthermore, circHIPK3 promoted metadherin (MTDH) expression by sponging miR-448. In vivo experiments, it was also found that overexpression of circHIPK3 significantly promoted tumor growth.

Conclusions: Our research shows that circHIPK3 plays a carcinogenic effect in PCa by regulating the miR-448/MTDH axis, indicating that circHIPK3 may be a potential therapeutic target for PCa.

Keywords: CircHIPK3; MTDH; MiR-448; Prostate cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Circular / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN448 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • HIPK3 protein, human
  • Protein Serine-Threonine Kinases