title: Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids.
abstract: Tumor stem cells with self-renewal and multipotent capacity play critical roles in the initiation and progression of cancer. Recently, a new 3-D culture system known as organoid culture has been developed, allowing Lgr5-positive stem cells to form organoids that resemble the properties of original tissues. Here we established organoids derived from intestinal tumors of Apcmin/+mice and normal intestinal epithelia of C57BL/6J mice and investigated the roles of microRNA (miRNA) in intestinal tumor organoids. The results of microarray analyses revealed that expression of the cluster miRNAs, miR-194 and miR-215 was markedly suppressed in intestinal tumor organoids in comparison with organoids derived from normal intestinal epithelia. Enforced expression of miR-194 resulted in inhibition of E2f3, a positive regulator of the cell cycle and growth suppression of intestinal tumor organoids. In addition, enforced expression of miR-215 suppressed the cancer stem cell signature through downregulation of intestinal stem cell markers including Lgr5. These findings indicate that the miRNA cluster including miR-194 and miR-215 plays important roles in suppressing the growth and attenuating the stemness of intestinal tumor organoids.
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakaoka
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Shimamoto
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Muramatsu
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Pathology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Minato-ku, Tokyo, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D066260:Epiregulin / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009924:Organ Culture Techniques; D009940:Organoids / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C498785:Ctnnbip1 protein, mouse; D050699:E2F3 Transcription Factor; C490840:E2f3 protein, mouse; D066260:Epiregulin; C587881:Ereg protein, mouse; C554845:MIRN194 microRNA, mouse; C577160:MIRN215 microRNA, mouse; D035683:MicroRNAs; D012097:Repressor Proteins; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Intestinal tumor; miR-194; miR-215; microRNA; organoid