miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells.
BACKGROUND
In recent years, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. In our previous studies, a set of miRNAs were revealed to be dysregulated in HCC tissues. However, the functions of these miRNAs in HCC remain largely undefined.


METHODS
The expression profiles of miR-183 were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was used to screen the potential target genes of miR-183. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-183 in hepatoma cells was examined.


RESULTS
Among the 25 HCC samples analyzed, microRNA-183 was significantly up-regulated (twofold to 367-fold) in 17 samples compared with the matching nontumoral liver tissues. Programmed cell death 4 (PDCD4) was identified as the target gene of miR-183. Moreover, PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, we found that miR-183 transfectants were resistant to apoptosis induced by TGF-beta1.


CONCLUSIONS
We conclude that miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development.
Li
Jipeng
J
Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, People's Republic of China.
Fu
Hanjiang
H
Xu
Chengwang
C
Tie
Yi
Y
Xing
Ruiyun
R
Zhu
Jie
J
Qin
Yide
Y
Sun
Zhixian
Z
Zheng
Xiaofei
X
D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053773:Transforming Growth Factor beta1; D008156:Luciferases