RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis

Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Vazganush Gharibyan, Kazuo Konishi, Elihu Estey, Hagop Kantarjian, Guillermo Garcia-Manero, Jean Pierre J. Issa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Gene silencing associated with promoter methylation can inactivate tumor suppressor genes (TSG) in cancer. We identified RIL, a LIM domain gene mapping to 5q31, a region frequently deleted in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), as methylated in 55 of 79 (70%) of cancer cell lines tested. In a variety of primary tumors, we found RIL methylation in 55 of 92 (60%) cases, with highest methylation in AML and colon cancer, and in 30 of 83 (36%) MDS samples, whereas normal tissues showed either absence or substantially lower levels of methylation, which correlates with age. RIL is ubiquitously expressed but silenced in methylated cancers and could be reactivated by the hypomethylating agent 5-aza-2′-deoxycytidine. Restoring RIL expression in colon cancer cells by stable transfection resulted in reduced cell growth and clonogenicity and an ∼ 2.0-fold increase in apoptosis following UV exposure. In MDS, RIL methylation is a marker of adverse prognosis independent of chromosome 5 and 7 deletions. Our data suggest that RIL is a good candidate TSG silenced by hypermethylation in cancer.

Original languageEnglish (US)
Pages (from-to)1997-2005
Number of pages9
JournalCancer Research
Volume67
Issue number5
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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