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MicroRNA-122a functions as a novel tumor suppressor downstream of adenomatous polyposis coli in gastrointestinal cancers
Authors:Xian Wang  Jianbin Zhang  Joseph J.Y. Sung
Affiliation:a Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, China
b Institute of Digestive Disease, Department of Medicine and Therapeutics, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Abstract:Aberrant regulation of APC/β-catenin signaling pathway is common in the pathogenesis of colorectal and other cancers. Targets regulated by APC/β-catenin signaling pathway play crucial roles in cancer development. In the current study, we aimed to illustrate the influence of APC/β-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/β-catenin signaling pathway. The down-regulation of miR-122a mediated by aberrant APC/β-catenin signaling is important to the pathogenesis of gastrointestinal cancers.
Keywords:microRNA   miR-122a   APC   Gastrointestinal cancers
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