title: Clinical significance of expression of Hint1 and potential epigenetic mechanism in gastric cancer.
abstract: HINT1, a member of the evolutionary highly conserved HIT protein superfamily, is ubiquitously expressed in diverse species including mammalian tissues. Accumulating evidence shows that HINT1 is a haploinsufficient tumor suppressor. In the present study, we explored possible correlations between the expression level of HINT1 and clinicopathological features in tissues from gastric cancer (GC) patients. Decreased expression of HINT1 detected by qPCR and Western blotting in tumor tissues was found in 58.82 and 39.2% of the patients, respectively. Significantly reduced expression of HINT1 was found in poorly differentiated tumor tissues (p = 0.027). Environmental interference (either H. pylori or EBV infection) (p = 0.005) was associated with the expression of HINT1. Moreover, compared with the GC tissues, the level of Hint1 detected by qPCR was significantly higher in the adjacent non-cancerous tissues (p = 0.03). We treated AGS cells, a GC cell line with low expression level of Hint1, with 5 and 10 µmol/l 5-Aza-dC for 72 h and found that HINT1 could be induced by 5-Aza-dC in a dose-dependent manner. These results suggested that Hint1 expression was lower in GC tissues and some etiological factors, such as H. pylori/EB infection or promoter hypermethylation may play a role in gastric tumorigenesis.
authors.affiliation: Department of Oncology, The Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China.
authors.forename: Huaying
authors.initials: H
authors.lastname: Huang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.forename: Xianwei
authors.initials: X
authors.lastname: Su
authors.forename: Fengchang
authors.initials: F
authors.lastname: Qiao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.forename: Dongying
authors.initials: D
authors.lastname: Gu
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000077209:Decitabine; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016481:Helicobacter Infections / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; C063306:HINT1 protein, human; D009419:Nerve Tissue Proteins; D000077209:Decitabine; D001374:Azacitidine