ZEB1-AS1 mediates bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer

Clin Respir J. 2024 May;18(5):e13770. doi: 10.1111/crj.13770.

Abstract

Objective: This study aimed to explore the role and regulatory mechanism of lncRNA ZEB1-AS1 in lung cancer.

Methods: The expression of ZEB1-AS1 and miR-320b was determined by qRT-PCR. Cell viability, proliferation migration, and invasion were assessed using the CCK-8, colony-forming, and Transwell assay. EMT markers were quantified using western blot. The growth of subcutaneous tumor growth and metastatic bone tumors was evaluated in mouse model of lung cancer. Additionally, metastatic bone tumors were examined using H&E staining.

Results: ZEB1-AS1 expression was upregulated, while miR-320b levels were downregulated in lung cancer. Knockdown of ZEB1-AS1 resulted in a significant suppression of cell viability, proliferation, migration, invasion, and EMT in A549 cells. Furthermore, we confirmed the targeting relationship between ZEB1-AS1 and miR-320b, as well as between miR-320b and BMPR1A. Our findings suggested that ZEB1-AS1 regulated cell viability, proliferation, migration, and invasion, as well as EMT, in lung cancer cells by targeting the miR-320b/BMPR1A axis. Moreover, our in vivo experiments confirmed that ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in mice with lung cancer.

Conclusion: ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer.

Keywords: ZEB1‐AS1; bone metastasis; lung cancer; miR‐320b.

MeSH terms

  • A549 Cells
  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Bone Neoplasms* / secondary
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • long non-coding RNA ZEB1-AS1, human
  • MicroRNAs
  • MIRN320 microRNA, human
  • RNA, Long Noncoding
  • Zinc Finger E-box-Binding Homeobox 1
  • BMPR1A protein, human