MILI, a PIWI family protein, inhibits melanoma cell migration through methylation of LINE1

Biochem Biophys Res Commun. 2015 Feb 20;457(4):514-9. doi: 10.1016/j.bbrc.2015.01.007. Epub 2015 Jan 10.

Abstract

MILI, a member of the PIWI/AGO gene family, has been well documented to maintain genome integrity by transposon silencing in animal germ cells. It has been reported to be selectively expressed in precancerous stem cells (pCSCs), tumor cell lines and various malignancies. However, the underlying mechanism remains largely unclear. Here, we found that MILI is expressed in the melanoma cell line B16 but not in the highly metastatic mouse melanoma model B16BL6. Interestingly, the knockdown of MILI in B16 could activate MAGEA expression and increase the cell migration ability, whereas the overexpression of MILI in B16BL6 could inhibit MAGEA expression and decrease the cell migration ability. Further investigations showed that MILI can methylate LINE1, which is crucial for MAGEA expression and melanoma cell migration. Our results provide a novel function of MILI in melanoma metastasis and tumor progression.

Keywords: LINE1; MAGEA; MILI; Melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • DNA Methylation*
  • Gene Expression Regulation, Neoplastic
  • Long Interspersed Nucleotide Elements*
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Neoplasm Proteins / genetics

Substances

  • Argonaute Proteins
  • Neoplasm Proteins
  • Piwil2 protein, mouse