As an example, the tumor suppressor Runt-related transcription factor 3 (RUNX3) is subject to EZH2induced methylation, which gene leads to down-regulation of RUNX3 messenger RNA (mRNA), promoting proliferation in multiple cancer cell lines.
Abbreviations: FOXC1, forkhead box C1; H3K27me3, H3K27 trimethylation; miRNAs, microRNAs; PAX8, paired box gene 8; PRC2, polycomb repressive complex 2; PSP94, prostate secretory protein of 94 amino acids; Rap1, Ras-proximate-1 or Ras-related protein 1; Rap1GAP, Rap1 GTPase-activating protein; RKIP, Raf-1 kinase inhibitor protein; RUNX3, Runt-related transcription factor 3 gene.
2009) revealed, for the first time, that the mRNA for RUNX3
, a tumor suppressor gene involved in several cancers, is suppressed in primary cutaneous melanoma and is further suppressed in metastatic tumors, as compared with normal tissue; and Nobeyama et al.
CD36 expression is down-modulated by RUNX3
overexpression (Puig-Kroger et al.
The team of 12 researchers at the state-run National University of Singapore and the Institute of Molecular and Cell Biology has found that the gene, known to scientists as RUNX3
, is disrupted at an early stage of colon cancer, said a joint statement issued by the institutions and several other agencies.
Merchant hypothesizes that inflammation brought on by excess bacterial growth might suppress RUNX3
Epigenetic inactivation of RUNX3
in microsatellite unstable sporadic colon cancers.
Associated with growth impairment was concomitant re-expression of multiple methylation-silenced tumor suppressor genes including p16ink4a and RUNX3
RUNX1 shares its DNA-binding properties with two other human proteins, RUNX2 and RUNX3
, although these two relatives aren't abundant in tissues that make immune cells.
Other cancer-related genes that have been shown to undergo abnormal methylation and induced gene silencing include RELN, (112) CCND2, (105) TFPI2, (113) RUNX3
, (114) SOCS 1, (115) and TSLC1/IGSF4.
121 The second study also included 46 PENs that were analyzed for 11 genes, 7 of which were common to both reports and showed the following methylation rates: RASSF1A (80%), P16/INK4A (0%), MGMT (17%), MLH1 (0%), APC (48%), E-cadherin (2%), TIMP3 (0%); the remaining 4 genes were MEN1 (19%), HIC-1 (93%), RUNX3
(7%), and PTEN (0%).
44) Several genes important in the pathogenesis of pancreatic cancer such as APC, (45) TSLC/IGSF4, (46) SOCS-1, (47) cyclin D2, (48) RASSF1A, (49) WWOX, (50) RUNX3
, (51) CDH13, (52) DUSP6, (53) HHIP, (54) and SLC5A8 (55) undergo aberrant methylation, leading to reduced expression or loss of expression.