MiR-520b promotes the progression of non-small cell lung cancer through activating Hedgehog pathway

J Cell Mol Med. 2019 Jan;23(1):205-215. doi: 10.1111/jcmm.13909. Epub 2018 Nov 8.

Abstract

Although the non-small cell lung cancer (NSCLC) is one of the most malignant tumours worldwide, the mechanisms controlling NSCLC tumourigenesis remain unclear. Here, we find that the expression of miR-520b is up-regulated in NSCLC samples. Further studies have revealed that miR-520b promotes the proliferation and metastasis of NSCLC cells. In addition, miR-520b activates Hedgehog (Hh) pathway. Inhibitor of Hh pathway could relieve the oncogenic effect of miR-520b upon NSCLC cells. Mechanistically, we demonstrate that miR-520b directly targets SPOP 3'-UTR and decreases SPOP expression, culminating in GLI2/3 stabilization and Hh pathway hyperactivation. Collectively, our findings unveil that miR-520b promotes NSCLC tumourigenesis through SPOP-GLI2/3 axis and provide miR-520b as a potential diagnostic biomarker and therapeutic target for NSCLC.

Keywords: NSCLC; SPOP; Hh pathway; miR-520b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Ubiquitination
  • Zinc Finger Protein Gli2 / genetics
  • Zinc Finger Protein Gli2 / metabolism
  • Zinc Finger Protein Gli3 / genetics
  • Zinc Finger Protein Gli3 / metabolism

Substances

  • 3' Untranslated Regions
  • GLI2 protein, human
  • GLI3 protein, human
  • Hedgehog Proteins
  • MIRN520 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • SPOP protein, human
  • Zinc Finger Protein Gli2
  • Zinc Finger Protein Gli3