Decreased EMILIN2 correlates to metabolism phenotype and poor prognosis of ovarian cancer

J Biochem. 2022 Jul 25;172(2):89-97. doi: 10.1093/jb/mvac046.

Abstract

This study aimed to explore the function and related mechanisms of elastin microfibril interfacer 2 (EMILIN2) in ovarian cancer. First, the expression level of EMILIN2 was detected in patient tissues and its correlation with overall survival rate was analysed. Then, EMILIN2 was overexpressed in ovarian cancer cell lines to observe its function and effect on Warburg effect. By detecting its promoter region methylation, the epigenetic regulatory role was explored. Finally, through the luciferase reporter assay and siRNA tools, the regulatory mechanism of p53 on EMILIN2 was investigated. It was detected in clinical samples that down-regulated EMILIN2 was associated with poor prognosis of ovarian cancer. It was further found that EMILIN2 regulated the metabolic phenotype of ovarian cancer cells. The expression of EMILIN2 was epigenetically regulated by its promoter methylation. Also, it was found that p53 regulated the expression of EMILIN2 and the p53/EMILIN2 axis regulated the Warburg effect in ovarian cancer cells. EMILIN2 was inhibited by methylation in ovarian cancer. In summary, p53 can promote and regulate its transcription by binding to the promoter region of EMILIN2, thereby affecting the Warburg effect and inhibiting tumours. Therefore, EMILIN2 might be a potential target for clinical diagnosis and treatment of ovarian cancer.

Keywords: P53; Warburg effect; glycolysis; metabolism; methylation.

MeSH terms

  • Cell Line, Tumor
  • DNA Methylation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins* / genetics
  • Humans
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / genetics
  • Phenotype
  • Prognosis
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • EMILIN2 protein, human
  • Glycoproteins
  • Tumor Suppressor Protein p53