CAVIN2 is frequently silenced by CpG methylation and sensitizes lung cancer cells to paclitaxel and 5-FU

Epigenomics. 2020 Oct;12(20):1793-1810. doi: 10.2217/epi-2020-0157. Epub 2020 Oct 5.

Abstract

Aim: To explore the biological functions and clinical significance of CAVIN2 in lung cancer. Materials & methods: Methylation-specific PCR was used to measure promoter methylation of CAVIN2. The function of CAVIN2 was tested by Cell Counting Kit-8, colony formation, Transwell, flow cytometric analysis, acridine orange/ethidium bromide, chemosensitivity assay and xenograft assay. Results: CAVIN2 is significantly downregulated by promoter methylation in lung cancer. CAVIN2 overexpression inhibits lung cancer cell migration and invasion. Furthermore, ectopic expression of CAVIN2 inhibits cell proliferation in vivo and in vitro by inducing G2/M cell cycle arrest, which sensitizes the chemosensitivity of lung cancer cells to paclitaxel and 5-fluorouracil, but not cisplatin. Conclusion: CAVIN2 is a tumor suppressor in non-small-cell lung cancer and can sensitize lung cancer cells to paclitaxel and 5-fluorouracil.

Keywords: CAVIN2; CpG methylation; cell cycle; non-small-cell lung cancer; paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • CpG Islands
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Methylation*
  • Female
  • Fluorouracil / therapeutic use*
  • G2 Phase Cell Cycle Checkpoints
  • Gene Silencing*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Mice, Nude
  • Neoplasm Invasiveness
  • Paclitaxel / therapeutic use*
  • Phosphate-Binding Proteins / genetics*
  • Phosphate-Binding Proteins / metabolism
  • Phosphate-Binding Proteins / physiology
  • Promoter Regions, Genetic

Substances

  • Antineoplastic Agents
  • CAVIN2 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Phosphate-Binding Proteins
  • Paclitaxel
  • Fluorouracil