Circular RNA circ-CBFB promotes proliferation and inhibits apoptosis in chronic lymphocytic leukemia through regulating miR-607/FZD3/Wnt/β-catenin pathway

Biochem Biophys Res Commun. 2018 Sep 3;503(1):385-390. doi: 10.1016/j.bbrc.2018.06.045. Epub 2018 Jun 15.

Abstract

Circular RNA (circRNA) belongs to the non-coding RNA family and is involved in various human cancers, such as lung cancer and colorectal cancer. Nevertheless, whether circRNA expression is related to chronic lymphocytic leukemia (CLL) progression remains largely unclear. In our study, we investigated the role of circ-CBFB in CLL. We found that circ-CBFB was markedly overexpressed in CLL cells compared to normal controls. Furthermore, we found that circ-CBFB could serve as a diagnostic and prognostic biomarker for CLL patients. We also explored the physiological function of circ-CBFB. We found that circ-CBFB knockdown significantly suppressed CLL cell proliferation, arrested cell cycle progression, and induced cellular apoptosis. In terms of its mechanism, we identified circ-CBFB as a sponge of miR-607, which targeted FZD3. By inhibiting miR-607 availability, circ-CBFB promoted FZD3 expression, leading to the activation of the Wnt/β-catenin pathway and consequent CLL progression. Taken together, our findings revealed that the circ-CBFB/miR-607/FZD3/Wnt/β-catenin regulatory signaling cascade contributes to CLL progression.

Keywords: Apoptosis; Chronic lymphocytic leukemia; Circ-CBFB; Proliferation.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Core Binding Factor beta Subunit / genetics*
  • Frizzled Receptors / genetics*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • MicroRNAs / metabolism*
  • RNA, Circular
  • Wnt Signaling Pathway

Substances

  • CBFB protein, human
  • Core Binding Factor beta Subunit
  • FZD3 protein, human
  • Frizzled Receptors
  • MIRN607 microRNA, human
  • MicroRNAs
  • RNA, Circular