title: Oncogenic KRAS regulates miR-200c and miR-221/222 in a 3D-specific manner in colorectal cancer cells.
abstract: BACKGROUND
  Oncogenic KRAS plays several key roles in a three-dimensional (3D) colonic-crypt model. However, miRNA expression regulated by oncogenic KRAS in this model is still elusive.
  
  
  METHODS
  The differential expression of 105 cancer-related microRNAs was examined and compared in HCT116 cells and HKe3 cells (HCT116 cells in which mutated KRAS allele was deleted) in 3D culture. HKe3 cells stably overexpressing oncogenic KRAS and the public datasets for microRNA expression analysis of colorectal cancer were further examined.
  
  
  RESULTS
  The increased expression of miR-200c, miR-221 and miR-222 were observed exclusively in 3D culture, but not in the two-dimensional culture. These microRNAs were regulated by oncogenic KRAS and were significantly overexpressed in human colorectal tumor specimens. Of note, the protein expression level of Phosphatase and tensin homolog (PTEN), a putative target of miR-221/222 cluster, was reduced under the control of oncogenic KRAS in a 3D-specific manner.
  
  
  CONCLUSIONS
  Oncogenic KRAS regulates 3D-specific molecules, possibly being associated with colorectal tumor development in vivo.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takashima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Keiko
authors.initials: K
authors.lastname: Doi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Machida
authors.forename: Takeharu
authors.initials: T
authors.lastname: Ota
authors.forename: Midori
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D018631:ras Proteins / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D051059:PTEN Phosphohydrolase; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D012334:RNA, Neoplasm; D018631:ras Proteins; C117307:KRAS protein, human; C525709:MIR221, human; C525710:MIR222, human; C494929:PTEN protein, human