title: Dicer 1, ribonuclease type III modulates a reprogramming effect in colorectal             cancer cells.
abstract: Complete cell reprogramming can be achieved by the introduction of specific transcription factors, Oct4 [also known as POU class 5 homeobox 1 (Pou5f1)]; sex-determining region Y (SRY)-box 2 (Sox2); Kruppel-like factor 4 (Klf4); and myelocytomatosis viral oncogene homolog (c-Myc), into terminally differentiated mouse somatic fibroblasts. This reprogramming process may be accelerated or suppressed by various factors, including microRNAs (miRNAs). Introduction of these transcription factors or miRNAs considerably modifies the malignant phenotype of cancer cells. We studied the effect of introducing these transcription factors into two distinct colorectal cancer (CRC) cell lines, HCT116 and DLD-1, in the presence and absence of Dicer 1, ribonuclease type III (Dicer1), a critical miRNA processing enzyme. We assessed cell reprogramming based on the number of cells exhibiting alkaline phosphatase staining and an increase in embryonic stem cell-like gene expression, indicating the return of cells to an immature state. Dicer1-deficient CRC cells showed a reduced number of alkaline phosphatase-positive reprogrammed cells than wild-type (WT) cells. Before reprogramming, endogenous expression of an immature carbohydrate epitope, TRA-1-60, was high in Dicer1-deficient CRC cells, whereas after reprogramming, the expression of this epitope was increased in Dicer1-sufficient more than in Dicer1-deficient CRC cells. Our data demonstrate the critical role of miRNAs in the reprogramming process and determination of a differentiated phenotype of CRC cells.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate                     School of Medicine, Osaka 565-0871, Japan.
authors.forename: Dyah Laksmi
authors.initials: DL
authors.lastname: Dewi
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.forename: Shimpei
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kano
authors.forename: Takahito
authors.initials: T
authors.lastname: Fukusumi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ozaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000201:enzymology; D000090062:Kruppel-Like Factor 4; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D011509:Proteoglycans / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D013194:Staining and Labeling; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D011509:Proteoglycans; C107064:TRA-1-60 antigen, human; D014157:Transcription Factors; C408087:DICER1 protein, human; D043244:Ribonuclease III; D000469:Alkaline Phosphatase; D053487:DEAD-box RNA Helicases