MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of β-catenin.
Mounting evidence has shown that microRNAs (miRNAs) are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. Recent profile studies of miRNA expression have documented a deregulation of miRNA (miR-214) in hepatocellular carcinoma (HCC). However, its potential functions and underlying mechanisms in hepatocarcinogenesis remain largely unknown. Here, we confirmed that miR-214 is significantly downregulated in HCC cells and specimens. Ectopic overexpression of miR-214 inhibited proliferation of HCC cells in vitro and tumorigenicity in vivo. Further studies revealed that miR-214 could directly target the 3'-untranslated region (3'-UTR) of β-catenin mRNA and suppress its protein expression. Similar to the restoring miR-214 expression, β-catenin downregulation inhibited cell growth, whereas restoring the β-catenin expression abolished the function of miR-214. Moreover, miR-214-mediated reduction of β-catenin resulted in suppression of several downstream genes including c-Myc, cyclinD1, TCF-1, and LEF-1. These findings indicate that miR-214 serves as tumor suppressor and plays substantial roles in inhibiting the tumorigenesis of HCC through suppression of β-catenin. Given these, miR-214 may serve as a useful prognostic or therapeutic target for treatment of HCC.
Liver Diseases Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Xiaojun
X
Wang
Ji
J
Chen
Feng
F
Li
Yanting
Y
Lin
Xiaoping
X
Zhang
Zhongwei
Z
Lv
Jiaji
J
Jiang
D020413:3' Untranslated Regions; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051822:T Cell Transcription Factor 1 / Q000235:genetics; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D020413:3' Untranslated Regions; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D051822:T Cell Transcription Factor 1; D051176:beta Catenin; D019938:Cyclin D1