Circ0001429 regulates progression of bladder cancer through binding miR-205-5p and promoting VEGFA expression

Cancer Biomark. 2019;25(1):101-113. doi: 10.3233/CBM-182380.

Abstract

Objective: This study investigates expressions of circ0001429, miR-205-5p and vascular endothelial growth factor (VEGFA) in bladder cancer tissues and their effects on the proliferation, migration and apoptosis.

Methods: Arraystar Human CircRNA chip was applied to analyzing the differential expression of circRNA in four bladder cancer tissues and paired adjacent normal bladder tissues. Real time quantitative PCR was utilized to detect the expression of circ0001429 in tissue specimens. Bioinformatics, RNA immunoprecipitation and luciferase reporter assays were used to verify the relationship among circ0001429, miR-205-5p and VEGFA in bladder cancer. Cell propagation was determined by CCK8 assay and roles of circ0001429 and miR-205-5p in cell migration were verified with transwell migration assay. Flow cytometry and TUNEL staining were conducted to observe the impact on cell apoptosis ability. Xenograft experiment was also performed to validate the influence of circ0001429 on tumor growth in vivo.

Results: Expressions of circ0001429 and VEGFA were up-regulated, whereas miR-205-5p expression was down-regulated in bladder cancer tissues in comparison with paired adjacent normal bladder tissues. Circ0001429 enhanced the propagation and metastasis abilities of T24 cells and 5637 cells in vitro, but reduced cell apoptosis. In vivo experiments revealed the inhibitor role of sh-circ0001429 in tumor growth and lung metastasis. Circ0001429 sponged miR-205-5p that targeted VEGFA, thereby modulating the protein level of VEGFA. Meanwhile, miR-205-5p restrained the cell viability and mobility and promoted the apoptosis in bladder cancer. Circ0001429 could accelerate cell propagation, migration and invasiveness through increasing VEGFA expression via miR-205-5p.

Conclusion: Circ0001429 and VEGFA were highly expressed in bladder cancer, while miR-205-5p were lowly expressed in bladder cancer. The circ0001429 could target at miR-205-5p to regulate VEGFA and promote the development of bladder cancer.

Keywords: Bladder cancer; VEGFA; circ0001429; miR-205-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • RNA / antagonists & inhibitors
  • RNA / genetics
  • RNA / metabolism*
  • RNA Interference
  • RNA, Circular
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • MIRN205 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • RNA