MicroRNA-122a functions as a novel tumor suppressor downstream of adenomatous polyposis coli in gastrointestinal cancers.
Aberrant regulation of APC/beta-catenin signaling pathway is common in the pathogenesis of colorectal and other cancers. Targets regulated by APC/beta-catenin signaling pathway play crucial roles in cancer development. In the current study, we aimed to illustrate the influence of APC/beta-catenin signaling pathway on expression of microRNAs, one new group of players important to carcinogenesis. Restoration of APC function in colorectal cancer cells led to the deregulation of several cancer-related microRNAs, such as miR-122a which was recognized as the liver-specific microRNA. MiR-122a was down-regulated in gastrointestinal cancer cell lines as well as primary carcinoma tissues. Inhibition of miR-122a could reverse wild-type APC-induced growth inhibition of gastrointestinal cancer cells while miR-122a mimic inhibited cell growth. In summary, we identified some cancer-related microRNAs regulated by APC/beta-catenin signaling pathway. The down-regulation of miR-122a mediated by aberrant APC/beta-catenin signaling is important to the pathogenesis of gastrointestinal cancers.
Wang
Xian
X
Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, China.
Lam
Emily K Y
EK
Zhang
Jianbin
J
Jin
Hongchuan
H
Sung
Joseph J Y
JJ
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism*
C495270:CTNNB1 protein, human; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin