MicroRNA-147b suppresses the proliferation and invasion of non-small-cell lung cancer cells through downregulation of Wnt/β-catenin signalling via targeting of RPS15A

Clin Exp Pharmacol Physiol. 2020 Mar;47(3):449-458. doi: 10.1111/1440-1681.13203. Epub 2019 Nov 24.

Abstract

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/β-catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/β-catenin signalling and suggest that the miR-147b/RPS15A/Wnt/β-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.

Keywords: Wnt; cancer; miR-147b; non-small-cell lung cancer; ribosomal protein S15A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / prevention & control
  • Cell Proliferation / physiology*
  • Down-Regulation / physiology
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control
  • MicroRNAs / biosynthesis*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Ribosomal Proteins / biosynthesis*
  • Wnt Signaling Pathway / physiology*

Substances

  • MIRN147 microRNA, human
  • MicroRNAs
  • RPS15A protein, human
  • Ribosomal Proteins