Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer

Biochem Biophys Res Commun. 2015 Aug 7;463(4):876-80. doi: 10.1016/j.bbrc.2015.06.028. Epub 2015 Jun 6.

Abstract

Piwil1, a member of the Piwi family, has been well demonstrated to mediate tumorigenesis associated with DNA hypermethylation. It has been reported that Piwil1 is overexpressed in various types of cancer, including endometrial cancer. However, the underlying mechanism of Piwil1 in endometrial cancer remains largely unclear. PTEN exerts an important tumor suppressor role in endometrial carcinogenesis. The present study aimed to investigate whether Piwil1 could regulate the expression of PTEN. Herein, we found that Piwil1 could promote the loss of PTEN expression and increase aberrant hypermethylation of PTEN gene promoter in Ishikawa cells. We also found that Piwil1 could regulate the expression of DNA methyltransferase 1 (DNMT1). Silencing DNMT1 gene could upregulate the PTEN gene expression and change the methylation status of PTEN gene promoter in Ishikawa cells. These results suggested that Piwil1 caused the loss of PTEN expression through DNMT1-mediated PTEN hypermethylation. Taken together, these data provide a novel regulatory mechanism of Piwil1 in endometrial cancer.

Keywords: DNA methylation; DNMT1; Endometrial cancer; PTEN; Piwil1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / physiology*
  • Base Sequence
  • Cell Line, Tumor
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / pathology
  • Epigenesis, Genetic / physiology*
  • Female
  • Humans
  • PTEN Phosphohydrolase / genetics*
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / genetics*

Substances

  • Argonaute Proteins
  • PIWIL1 protein, human
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human