CircABCB10 promotes nonsmall cell lung cancer cell proliferation and migration by regulating the miR-1252/FOXR2 axis

J Cell Biochem. 2019 Mar;120(3):3765-3772. doi: 10.1002/jcb.27657. Epub 2018 Nov 11.

Abstract

Circular RNA (circRNA) is a key regulator in the development and progression of human cancers. Previous studies confirmed circRNA-0008717 (circABCB10) as an oncogene in osteosarcoma, but the regulatory effect of circABCB10 in nonsmall cell lung cancer (NSCLC) is still unclear. In the current study, we examined the expression of circABCB10 in different NSCLC cell lines. Bioinformatics analysis, Cell Counting Kit-8 assays, Transwell migration, fluorescein reporting experiments, and xenografts in mice were used to detect the effect of circABCB10 on NSCLC cell proliferation and migration in vitro and tumor growth in vivo. The results showed that the expression of circABCB10 in NSCLC cell lines was increased. Downregulation of circABCB10 suppressed NSCLC cell proliferation and migration by promoting microRNA miR-1252 expression and suppressing Forkhead box 2 (FOXR2). Fluorescein reporting experiments confirmed that circABCB10 expression increased FOXR2 levels by sponging miR-1252, and in vivo experiments found that knockdown of circABCB10 decreased tumor growth. These data suggested that circABCB10 acted as a tumor promoter through a novel miR-1252/FOXR2 axis, providing potential biomarkers and therapeutic targets for the management of NSCLC.

Keywords: FOXR2; circABCB10; miR-1252; nonsmall cell lung cancer; proliferation and migration.

MeSH terms

  • A549 Cells
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • RNA, Circular / antagonists & inhibitors
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • ABCB10 protein, human
  • ATP-Binding Cassette Transporters
  • FOXR2 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering