Elevated expression of circular RNA circ_0008450 predicts dismal prognosis in hepatocellular carcinoma and regulates cell proliferation, apoptosis, and invasion via sponging miR-548p

J Cell Biochem. 2019 Jun;120(6):9487-9494. doi: 10.1002/jcb.28224. Epub 2018 Dec 16.

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and a main cause of global cancer mortality. In the past decade, circular RNAs (circRNAs) have been proved to play key roles in various cancers. Previously, circ_0008450 was identified upregulated in HCC tissues by high-throughput circRNA sequencing. In this study, quantitative real-time polymerase chain reaction was used to evaluate the expression level of circ_0008450 in human HCC tumor and corresponding nontumor tissue samples, and the association between circ_0008450 expression and clinicopathologic features of patients with HCC was also analyzed. After that, the functions of circ_0008450 in biological behaviors of HCC cells were determined by cell counting kit-8, colony formation, flow cytometry, and the transwell assays. The mechanism of circ_0008450 was explored by the bioinformatic analysis and dual-luciferase reporter assay. The expression of circ_0008450 is upregulated in HCC tissue specimens and cell lines. Patients with a high circ_0008450 expression usually bear a lower 5-year survival rate. Silencing of circ_0008450 in Huh-7 cells inhibited cell viability, migration, and invasion, whereas cell apoptosis was increased. Conversely, its overexpression in HepG2 cells leads to absolutely inverse results. In addition, circ_0008450 was proved to be a sponge of miR-548p. The oncogenic role of circ_0008450 was partially attributed to its suppression on miR-548p. This study implies a new target for the treatment of HCC.

Keywords: circ_0008450; circular RNA; hepatocellular carcinoma; miR-548p; prognosis.

MeSH terms

  • Aged
  • Apoptosis / genetics*
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Survival Analysis

Substances

  • MIRN548 microRNA, human
  • MicroRNAs
  • RNA, Circular