Promoter hypermethylation mediates downregulation of thiamine receptor SLC19A3 in gastric cancer.
As an important way to inactivate tumor suppressor genes (TSGs) during cancer development, promoter hypermethylation can be used to define novel TSGs and identify biomarkers for cancer diagnosis. SLC19A3 (solute carrier family 19, member 3) was found to be such a biomarker. SLC19A3 expression was downregulated in gastric cancer cell lines (71%, 5/7) and restored after pharmacological demethylation. Notably, hypermethylation of SLC19A3 promoter was detected in gastric cancer cell lines (57%, 4/7), primary gastric carcinoma tissues (51%, 52/101) and precancerous lesion (intestinal metaplasia) tissues (32%, 8/25). Exogenous SLC19A3 expression caused growth inhibition of gastric cancer cells. In summary, SLC19A3 was epigenetically downregulated in gastric cancer. Methylation of SLC19A3 promoter could be a novel biomarker for early gastric cancer development.
Liu
Xin
X
Institute of Digestive Disease, Department of Medicine and Therapeutics, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Lam
Emily K Y
EK
Wang
Xian
X
Zhang
Jianbin
J
Cheng
Yuen Yee
YY
Lam
Yun W
YW
Ng
Enders K O
EK
Yu
Jun
J
Chan
Francis K L
FK
Jin
HongChuan
H
Sung
Joseph J Y
JJ
D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors
D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human