microRNA-150 inhibits human CD133-positive liver cancer stem cells through             negative regulation of the transcription factor c-Myb.
MicroRNAs (miRNAs) have been implicated in the maintenance of the cancer             stem cell (CSC) phenotype via their ability to affect expression of genes and             proteins that regulate cell proliferation and/or cell death. Thus, identification             of CSC-related miRNAs would provide information for a better understanding of             CSCs. Here, we compared the miRNA profiles of CD133+ and CD133- primary hepatocellular             carcinoma (HCC) subpopulations and found upregulation of 5 miRNAs in CD133- subpopulations,             including hsa-miR-150, which may be involved in maintenance of the CD133+ liver             CSC phenotype. We also show that miR-150 interacts with the 3'UTR of c-Myb mRNA             and overexpression of miR-150 downregulates c-Myb protein levels. Furthermore,             overexpression of miR-150 lead to a significant reduction of CD133+ cells, accompanied             by significant inhibition of cell growth and tumorsphere formation. In addition,             overexpression of miR-150 induces cell cycle arrest and apoptosis in CD133+ cells.             Consistent with the outcome of cell cycle arrest and cell apoptosis, Western blotting             results demonstrate that the cell cycle regulator cyclin D1 and cell survival             regulator Bcl-2 are decreased in cells transfected with miR-150. Collectively,             our findings demonstrate for the first time that miR-150 may be involved in liver             CSC self-renewal, potentially via modulation of the downstream target c-Myb.
Department of Radiology, Chongqing Medical University, Chongqing, People's Republic of China.
Jun
J
Zhang
Na
N
Luo
Yi
Y
Luo
Zhiping
Z
Peng
Tao
T
Zhang
Shaolin
S
Li
D020413:3' Untranslated Regions / Q000235:genetics; D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D020413:3' Untranslated Regions; D000071916:AC133 Antigen; D015703:Antigens, CD; D019938:Cyclin D1; D006023:Glycoproteins; D035683:MicroRNAs; D010455:Peptides; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; C530104:CCND1 protein, human; C533097:MIR150, human; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse