Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer.
Aberrant DNA methylation is considered a major mechanism for silencing tumor suppressor genes in gastric cancer. We used CpG microarray and differential methylation hybridization strategies to identify potential tumor suppressor genes and recovered glutamate receptor, ionotropic, kainate 2 (GRIK2) as a novel epigenetic target in gastric cancer. Additional experiments showed that the promoter region of GRIK2 was hypermethylated in 3 of the 4 tested gastric cancer cell lines, and its expression was restored by treatment of cells with the DNA methylation inhibitor, 5'-aza-dC. In clinical samples, the GRIK2 promoter was differentially hypermethylated in tumor tissues compared with adjacent normal tissues (p < 0.001), and this methylation was inversely correlated with the expression level of GRIK2 mRNA (r = -0.44). Functional studies further showed that GRIK2-expressing gastric cancer cell lines showed decreased colony formation and cell migration. Taken together, these results suggest that GRIK2 may play a tumor-suppressor role in gastric cancer. Future studies are warranted to examine whether DNA hypermethylation of the GRIK2 promoter can be used as a potential tumor marker for gastric cancer.
Wu
Chi-Sheng
CS
Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
Lu
Yen-Jung
YJ
Li
Hsin-Pai
HP
Hsueh
Chuen
C
Lu
Chang-Yi
CY
Leu
Yu-Wei
YW
Liu
Hao-Ping
HP
Lin
Kwang-Huei
KH
Hui-Ming Huang
Tim
T
Chang
Yu-Sun
YS
D000368:Aged; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003114:Colony-Forming Units Assay; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018092:Kainic Acid Receptors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013489:Suppression, Genetic; D014162:Transfection; D000097806:GluK2 Kainate Receptor
D017931:DNA Primers; D004273:DNA, Neoplasm; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor