Enhanced expression of circular RNA circ-DCAF6 predicts adverse prognosis and promotes cell progression via sponging miR-1231 and miR-1256 in gastric cancer

Exp Mol Pathol. 2019 Oct:110:104273. doi: 10.1016/j.yexmp.2019.104273. Epub 2019 Jun 19.

Abstract

Circular RNAs (circRNAs) have been reported as essential regulators in various malignancies, including gastric cancer (GC). Previously, circ-DCAF6 was screened as an elevated circRNA in GC patients' tissue samples compared with the normal tissues. To our knowledge, the role of circ-DCAF6 in human cancers is still needed to reveal. The present project is to evaluate the functions and mechanisms of circ-DCAF6 in GC progression. Upregulation of circ-DCAF6 was determined in GC tissue samples and cells by qRT-PCR. Enhanced level of circ-DCAF6 was linked to deeper tumor invasion, positive lymph node metastasis, and higher TNM stages in GC patients. Multivariate analysis further indicated circ-DCAF6 as an independent prognostic indicator. Functionally, CCK-8, clone forming, flow cytometry and transwell assays verified that circ-DCAF6 played as an oncogene in GC cells. Mechanistically, we found the negative correlation between circ-DCAF6 and miR-1231/-1256 in GC specimens. Moreover, luciferase reporter gene assay illustrated that miR-1231 and miR-1256 could be bound to circ-DCAF6. Rescue experiments revealed that circ-DCAF6 facilitated cell growth and invasion via suppressing the levels of miR-1231 and miR-1256. To sum up, circ-DCAF6 acts as an important role in GC tumor progression, and high circ-DCAF6 level may be a useful biomarker for GC.

Keywords: Circ-DCAF6; Gastric cancer; circRNA; miR-1231; miR-1256.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Prognosis
  • RNA, Circular / genetics*
  • Sequence Homology, Nucleic Acid
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • DCAF6 protein, human
  • MIRN1231 microRNA, human
  • MIRN1256 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Circular