miR-154 targeting ZEB2 in hepatocellular carcinoma  functions as a potential tumor suppressor.
MicroRNA-154 (miR-154) has been identified as a tumor suppressor in several types of human cancers; however, its clinical significance and function in human hepatocellular carcinoma (HCC) remain unclear. The aim of the present study was to analyze the clinical significance and cellular function of miR-154 in HCC patients. The data showed that miR-154 expression was consistently lower in HCC tissues and cell lines compared to that in matched tumor-adjacent tissues and a normal hepatic cell line, and its expression was negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Restoration of miR-154 expression in HepG2 cells inhibited cell proliferation, migration and invasion, and induced apoptosis and cell arrest at the G1 phase in vitro, as well as suppressed tumor growth in a nude mouse model. Using a luciferase assay, we identified that miR-154 was able to target the 3'-untranslated region (3'UTR) of ZEB2 mRNA. Then, we revealed that miR-154 was able to reduce ZEB2 expression at the levels of mRNA and protein using qRT-PCR and western blot analysis. Notably, restoration of expression of ZEB2 weakened miR-154-mediated suppression of tumor progression. In conclusion, these results indicate that miR-154 functions as a tumor suppressor in HCC by suppressing ZEB2, suggesting that miR-154 may serve as a potential target for HCC.
Xiaoli
X
Pang
Kexin
K
Huang
Qianqian
Q
Zhang
Yujiao
Y
Zhang
Junqi
J
Niu
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2
D018398:Homeodomain Proteins; C561122:MIRN154 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2