title: Dynamics and plasticity of the epithelial to mesenchymal transition induced by miR-200 family inhibition.
abstract: Whereas miR-200 family is known to be involved in the epithelial-to-mesenchymal transition (EMT), a crucial biological process observed in normal and pathological contexts, it has been largely unclear how far the functional levels of these tiny RNAs alone can propagate the molecular events to accomplish this process within several days. By developing a potent inhibitor of miR-200 family members (TuD-141/200c), the expression of which is strictly regulatable by the Tet (tetracycline)-On system, we found using a human colorectal cell line, HCT116, that several direct gene target mRNAs (Zeb1/Zeb2, ESRP1, FN1and FHOD1) of miR-200 family were elevated with distinct kinetics. Prompt induction of the transcriptional suppressors, Zeb1/Zeb2 in turn reduced the expression levels of miR-200c/-141 locus, EpCAM, ESRP1 and E-Cad. The loss of ESRP1 subsequently switched the splicing isoforms of CD44 and p120 catenin mRNAs to mesenchymal type. Importantly, within 9 days after the release from the inhibition of miR-200 family, all of the expression changes in the 14 genes observed in this study returned to their original levels in the epithelial cells. This suggests that the inherent epithelial plasticity is supported by a weak retention of key regulatory gene expression in either the epithelial or mesenchymal states through epigenetic regulation.
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Haraguchi
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Uchikawa
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiramatsu
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ung Weng
authors.initials: UW
authors.lastname: Chit
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo Div. Host-Parasite Interaction, Int. Med. Sci., Univ. Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Iba
mesh_terms: D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs