Circular RNA circABCC4 regulates lung adenocarcinoma progression via miR-3186-3p/TNRC6B axis

J Cell Biochem. 2020 Oct;121(10):4226-4238. doi: 10.1002/jcb.29627. Epub 2020 Jan 21.

Abstract

Lung adenocarcinoma (LUAD), a general kind of bronchogenic malignancy globally, is depicted as one of the most critical factors affecting human health severely. Featured with loop structure, circular RNA (circRNA) has been described as an essential regulator of multiple human malignancies. Nevertheless, knowledge concerning the regulatory function of circRNA in LUAD progression remains limited. Identified as a novel circRNA, circABCC4 has not been studied in LUAD as yet. This is the first time to probe into the underlying role of circABCC4 in LUAD. In this study, a notably elevated expression of circABCC4 was found in LUAD tissues and cells. Besides, circABCC4 is verified to be characterized with a circular structure in LUAD. Functional assays elucidated that knockdown of circABCC4 significantly impaired LUAD cell proliferation, migration as well as accelerated cell apoptosis. Molecular mechanism experiments later revealed that circABCC4 could bind with miR-3186-3p and miR-3186-3p was a tumor suppressor in LUAD. Moreover, TNRC6B was validated to combine with miR-3186-3p, and its expression was respectively negatively and positively regulated by miR-3186-3p and circABCC4 in LUAD. Final rescue experiments further delineated that TNRC6B upregulation partially restored circABCC4 downregulation-mediated effect on LUAD progression. In sum, circABCC4 regulates LUAD progression via miR-3186-3p/TNRC6B axis.

Keywords: LUAD; TNRC6B; circABCC4; miR-3186-3p.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multidrug Resistance-Associated Proteins / genetics*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / genetics*
  • Transfection
  • Tumor Burden / genetics
  • Xenograft Model Antitumor Assays

Substances

  • ABCC4 protein, human
  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • RNA, Circular
  • RNA-Binding Proteins
  • TNRC6B protein, human