CBX4/miR-190 regulatory loop inhibits lung cancer metastasis

Thorac Cancer. 2024 Sep;15(26):1889-1896. doi: 10.1111/1759-7714.15415. Epub 2024 Aug 4.

Abstract

Background: Lung cancer is one of the major threats to human life worldwide. MiR-190 has been found to perform essential roles in multiple cancer progression; however, there have been no studies focused on its function and underlying regulatory mechanism in lung cancer.

Method: The miR-190 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The cell functional experiments, including cell counting kit-8 (CCK-8), colony formation and transwell assay were conducted in vitro, as well as animal experiments performed in vivo. The regulation and potential binding sites of CBX4 on miR-190 were predicted by TCGA data set and JASPAR website and verified by ChIP assay and dual-luciferase reporter assay. The prospects binding site of miR-190-3p on CBX4 3'UTR region was predicted by StarBase and verified by dual-luciferase reporter assay.

Results: MiR-190 was decreased in lung cancer cells. The overexpression of miR-190 had no effects on cell proliferation, but significantly inhibited cancer metastasis both in vitro and in vivo. Moreover, miR-190 expression could be transcriptionally inhibited by CBX4, and CBX4 was the direct target of miR-190-3p.

Conclusion: MiR-190 served as a cancer metastasis inhibitor in lung cancer and formed a regulatory loop with CBX4. These findings provided emerging insights into therapeutic targets and strategies for metastatic lung cancer.

Keywords: CBX4; lung cancer; metastasis; miR‐190.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ligases / genetics
  • Ligases / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Neoplasm Metastasis
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • CBX4 protein, human
  • Ligases
  • MicroRNAs
  • Polycomb-Group Proteins
  • MIRN190 microRNA, human