Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma

Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8274-8286. doi: 10.26355/eurrev_201910_19138.

Abstract

Objective: Various studies have shown that aberrant expression of circular RNAs (circRNAs) has a pivotal role in multifarious cancers. However, the role of circRNAs in hepatoblastoma (HB) is not clearly understood. In the present study, we attempted to explore the underlying mechanism of hsa_cric_0000594 in HB along with its clinical importance.

Patients and methods: In our research, the expression pattern of hsa_circ_0000594 in HB tissues and matched normal liver tissues was determined by in situ hybridization and RT-qPCR. Proliferation, viability, migration, and apoptosis of HB cell lines were detected via Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays. The interaction of hsa_circ_0000594 with miR-217 was investigated by Dual-Luciferase reporter assay.

Results: Expression levels of hsa_circ_0000594 were significantly upregulated in HB tissues compared with those in paired normal liver tissues and showed a clear association with the subtype of HB. The knockdown of hsa_circ_0000594 inhibited the malignant phenotype of HB. Bioinformatics analysis suggests that sirtuin 1 (SIRT1) may serve as a target gene of miR-217.

Conclusions: Mechanically, hsa_circ_0000594 was identified to have a critical role in HB development through the hsa_circ_0000594/mir-217/SIRT1 regulatory axis, which might become a novel diagnostic marker and potential therapeutic target in HB.

MeSH terms

  • Apoptosis
  • Biomarkers
  • Blotting, Western
  • Cell Line, Tumor
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Hepatoblastoma / metabolism*
  • Hepatoblastoma / pathology
  • Humans
  • In Situ Hybridization
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MicroRNAs / metabolism
  • RNA, Circular / metabolism*
  • RNA, Neoplasm / metabolism*
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers
  • MIRN217 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Neoplasm