MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma.
MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of various biological processes. Although there is emerging evidence that some microRNAs can function as oncogenes or tumor suppressors, the specific role of miRNA in human hepatocellular carcinoma (HCC) is unclear at this point. In this study, we examined the microRNA expression profiles in a set of 20 human HCC specimens by miRNA microarray and quantitative real-time polymerase chain reaction. The results showed that among the 20 HCC samples analyzed, microRNA-101 was significantly down-regulated twofold or more (twofold to 20-fold) in 16 samples compared with the matching nontumoral liver tissues. Using both a luciferase reporter assay and Western blot analysis, we showed that microRNA-101 repressed the expression of v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene, a key component of the activator protein-1 (AP-1) transcription factor. Moreover, using a luciferase expression vector (pAP-1-Luc) driven by seven copies of an AP-1 cis-element, we observed that microRNA-101 expression inhibited phorbol 12-myristate 13-acetate (PMA)-induced AP-1 activity. In in vitro Matrigel invasion and Transwell migration assays, enhanced microRNA-101 expression inhibited the invasion and migration of cultured HCC cells, respectively. These findings suggest that microRNA-101 may play an important role in HCC.


CONCLUSIONS
MicroRNA-101, which is aberrantly expressed in HCC, could repress the expression of the FOS oncogene.
Li
Shuai
S
Beijing Institute of Radiation Medicine, Beijing, China.
Fu
Hanjiang
H
Wang
Yulan
Y
Tie
Yi
Y
Xing
Ruiyun
R
Zhu
Jie
J
Sun
Zhixian
Z
Wei
Lixin
L
Zheng
Xiaofei
X
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016762:Genes, fos; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000378:metabolism
D020413:3' Untranslated Regions; C064269:FOSB protein, human; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D000073718:Pancreatitis-Associated Proteins; D016760:Proto-Oncogene Proteins c-fos; C000612141:REG3A protein, human; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D013755:Tetradecanoylphorbol Acetate