CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway

Biochem Biophys Res Commun. 2019 Jan 1;508(1):37-45. doi: 10.1016/j.bbrc.2018.11.079. Epub 2018 Nov 20.

Abstract

Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783-3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/β-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783-3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783-3p/DKK1 axis.

Keywords: DKK1; Lung adenocarcinoma; circ_0006427; miR-6783–3p.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Models, Molecular
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Nucleic Acid Conformation
  • Prognosis
  • RNA / chemistry
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • RNA, Neoplasm / chemistry
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs
  • RNA, Circular
  • RNA, Neoplasm
  • beta Catenin
  • RNA