An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese.
Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFkappaB signaling pathway, beta-transducin repeat-containing protein (betaTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of betaTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9bp insertion/deletion polymorphism (rs16405) in 3' untranslated region of betaTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR=0.44 (0.24-0.83) (p=0.004) and OR=0.56 (0.31-1.00) (p=0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of betaTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of betaTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which would negatively regulate betaTrCP. We propose a microRNA-920 mediated betaTrCP regulation model depending on rs16405 genotype, which warrants further replication association studies and follow-up functional experiments.
Chen
Shougong
S
Department of Forensic Medicine, Medical College of Soochow University, Suzhou, 215123 Jiangsu, PR China.
He
Yan
Y
Ding
Jun
J
Jiang
Yuting
Y
Jia
Shasha
S
Xia
Wei
W
Zhao
Ji
J
Lu
Man
M
Gu
Zhenyong
Z
Gao
Yuzhen
Y
D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics*
D020413:3' Untranslated Regions; C471644:BTRC protein, human; D035683:MicroRNAs; D044844:beta-Transducin Repeat-Containing Proteins