EHMT2 promotes the development of prostate cancer by inhibiting PI3K/AKT/mTOR pathway

Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7808-7815. doi: 10.26355/eurrev_201909_18990.

Abstract

Objective: To investigate the expression characteristics and the potential role of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) in the clinical pathology and prognosis of prostate cancer (PCa).

Patients and methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of EHMT2 in 55 pairs of PCa tissues and adjacent normal tissues. The relationship between EHMT2 expression and the pathological features, as well as the prognosis of PCa patients was analyzed. EHMT2 expression in PCa cells was determined by qRT-PCR as well. In addition, EHMT2 knockdown model was constructed by transfection of the small interfering RNA in PCa cell lines PC-3 and DU-145. The regulatory effects of EHMT2 on the behaviors of PCa cells were evaluated through cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay and flow cytometry. Finally, we detected the protein levels of relative genes in PI3K/AKT/mTOR pathway through Western blot.

Results: QRT-PCR results showed that the expression level of EHMT2 in PCa tissues was markedly higher than that in adjacent normal tissues. Compared with PCa patients with low expression of EHMT2, those with high expression of EHMT2 had higher pathological grade and lower overall survival. EHMT2 was also highly expressed in PCa cell lines. Knockdown of EHMT2 inhibited the proliferative potential and induced apoptosis of PCa cells. Western blot results revealed that PCa cells with EHMT2 knockdown presented downregulated p-PI3K, p-AKT and p-mTOR.

Conclusions: EHMT2 was highly expressed in PCa, and its expression is closely correlated with tumor stage and poor prognosis of PCa patients. EHMT2 promoted the malignant progression of PCa by inhibiting PI3K/AKT/mTOR pathway.

MeSH terms

  • Aged
  • Apoptosis
  • Case-Control Studies
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Disease Progression
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens / genetics*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging / methods
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / pharmacology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Histocompatibility Antigens
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • EHMT2 protein, human
  • Histone-Lysine N-Methyltransferase
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases